Systems and methods for therapeutic nasal neuromodulation

ABSTRACT

The invention generally relates to systems and methods for therapeutically modulating nerves in or associated with a nasal region of a patient for the treatment of a rhinosinusitis condition.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to, and the benefit of, U.S.Provisional Application No. 62/778,233, filed Dec. 11, 2018, U.S.Provisional Application No. 62/832,914, filed Apr. 12, 2019, U.S.Provisional Application No. 62/832,917, filed Apr. 12, 2019, U.S.Provisional Application No. 62/832,918, filed Apr. 12, 2019, U.S.Provisional Application No. 62/832,920, filed Apr. 12, 2019, U.S.Provisional Application No. 62/832,923, filed Apr. 12, 2019, U.S.Provisional Application No. 62/832,925, filed Apr. 12, 2019, U.S.Provisional Application No. 62/832,927, filed Apr. 12, 2019, U.S.Provisional Application No. 62/832,928, filed Apr. 12, 2019, U.S.Provisional Application No. 62/896,845, Sep. 6, 2019, the contents ofeach of which are incorporated by reference herein in their entireties.

FIELD OF THE INVENTION

The invention generally relates to systems and methods for treatingmedical conditions, and, more particularly, to therapeuticallymodulating nerves in a nasal region of a patient for the treatment of arhinosinusitis condition.

BACKGROUND

Rhinitis is an inflammatory disease of the nose and is reported toaffect up to 40% of the population. It is the fifth most common chronicdisease in the United States. The most common and impactful symptoms ofrhinitis are congestion and rhinorrhea. Allergic rhinitis accounts forup to 65% of all rhinitis patients. Allergic rhinitis is an immuneresponse to an exposure to allergens, such as airborne plant pollens,pet dander or dust. Non-allergic rhinitis is the occurrence of commonrhinitis symptoms of congestion and rhinorrhea. As non-allergic rhinitisis not an immune response, its symptoms are not normally seasonal andare often more persistent. The symptoms of rhinitis include a runnynose, sneezing, and nasal itching and congestion.

Allergen avoidance and pharmacotherapy are relatively effective in themajority of mild cases, but these medications need to be taken on along-term basis, incurring costs and side effects and often havesuboptimal efficacy. For example, pharmaceutical agents prescribed forrhinosinusitis have limited efficacy and undesirable side effects, suchas sedation, irritation, impairment to taste, sore throat, dry nose, andother side effects.

There are two modern surgical options: the delivery of thermal energy tothe inflamed soft tissue, resulting in scarring and temporary volumetricreduction of the tissue to improve nasal airflow; and microdebriderresection of the inflamed soft tissue, resulting in the removal oftissue to improve nasal airflow. Both options address congestion asopposed to rhinorrhea and have risks ranging from bleeding and scarringto the use of general anesthetic.

SUMMARY

The invention recognizes that a problem with current surgical proceduresis that such procedures are not accurate and cause significantcollateral damage in order to treat rhinitis. The invention solves thatproblem by providing devices having a unique multi-stage end effectorand a handle architecture that provides a high level of precise controland feedback to an operator during use of the devices of the invention.The multi-stage end effector is configured to complement anatomy atmultiple different locations within the nasal cavity. The handle isconfigured with multiple ergonomic and functional features that improvedevice use and feedback, such as independent control of deployment ofthe end effector and energy delivery and a shape associated with thearchitecture of the end effector in the deployed configuration. Thehandle may also include one or more markings that provide a user with aspatial orientation of the end effector while the end effector is in anasal cavity. In that manner, the present invention provides devicesthat are capable of highly conforming to anatomical variations within anasal cavity while providing unprecedented control and guidance to anoperator so that an operator can perform an accurate, minimallyinvasive, and localized application of energy to one or more targetsites within the nasal cavity to cause multi-point interruption ofneural signal without causing collateral damage or disruption to otherneural structures.

Unlike other surgical treatments for rhinitis, the devices of theinvention are minimally invasive. Accordingly, a procedure can beperformed in an office environment under local anesthetic. Themulti-stage end-effector allows for targeting the autonomic supply tothe nasal turbinates and will have a positive impact on both allergicand non-allergic rhinitis. Using this approach, it is expected thatdevices of the invention will be able to provide long-term symptomrelief (e.g., years instead of months). Since the treatment is accuratewith minimal collateral damage to the surrounding tissue, patients willbegin to feel symptom relief immediately following the treatment. It isfully expected that patients will be removed from theirpharmacotherapies following this therapy.

The systems and methods of the present invention include a handhelddevice comprising a retractable and expandable multi-segment endeffector that, once delivered to the one more target sites within thenasal cavity, can expand to a specific shape and/or size correspondingto anatomical structures within the nasal cavity and associated with thetarget sites. In particular, the end effector includes at least a firstflexible segment and a second flexible segment, each of which includes aspecific geometry when in a deployed configuration to complement anatomyof respective locations within the nasal cavity. Once deployed, thefirst and second segments contact and conform to a shape of therespective locations, including conforming to and complementing shapesof one or more anatomical structures at the respective locations. Inturn, the first and second segments become accurately positioned withinthe nasal cavity to subsequently deliver, via one or more electrodes,precise and focused application of RF thermal energy to the one or moretarget sites to thereby therapeutically modulate associated neuralstructures. More specifically, the first and second segments have shapesand sizes when in the expanded configuration that are specificallydesigned to place portions of the first and second segments, and thusone or more electrodes associated therewith, into contact with targetsites within nasal cavity associated with postganglionic parasympatheticfibers that innervate the nasal mucosa.

The handheld device further includes a shaft operably associated withthe end effector and a handle operably associated with the shaft. Theshaft may include a pre-defined shape (i.e., bent or angled at aspecific orientation) so as to assist the surgeon (or other medicalprofessional) for placement of the end effector at the target sites. Thehandle includes an ergonomically-designed grip portion which providesambidextrous use for both left and right handed use and conforms to handanthropometrics to allow for at least one of an overhand grip style andan underhand grip style during use in a procedure. The handle furtherincludes multiple user-operated mechanisms, including at least a firstmechanism for deployment of the end effector from the retractedconfiguration to the expanded deployed configuration and a secondmechanism for controlling of energy output by the end effector. The userinputs for the first and second mechanisms are positioned a sufficientdistance to one another to allow for simultaneous one-handed operationof both user inputs during a procedure. Accordingly, the handleaccommodates various styles of grip and provides a degree of comfort forthe surgeon, thereby further improving execution of the procedure andoverall outcome. Furthermore, the handle and/or the shaft may includemarkings (e.g., text, symbols, color-coding insignia, etc.) that providea surgeon with a spatial orientation of the end effector while the endeffector is in a nasal cavity. In particular, multiple markings may beprovided on the handle and/or shaft and provide a visual indication ofthe spatial orientation of one or more portions of the first segment andsecond segment of the end effector when in the deployed configurations.Thus, during initial placement of the end effector, when in a retractedconfiguration and enclosed within the shaft, a surgeon can rely on themarkings on the handle and/or shaft as a visual indication of thespatial orientation of the end effector (e.g., linear, axial, and/ordepth position) prior to deployment to thereby ensure that, oncedeployed, the end effector, including both the first and secondsegments, are positioned in the intended locations within the nasalcavity.

Accordingly, the handheld device of the present invention provides auser-friendly, non-invasive means of treating rhinosinusitis conditions,including precise and focused application of RF thermal energy to theintended target sites for therapeutic modulation of the intended neuralstructures without causing collateral and unintended damage ordisruption to other neural structures. Thus, the efficacy of a vidianneurectomy procedure can be achieved with the systems and methods of thepresent invention without the drawbacks discussed above. Most notably,the handheld device provides a surgeon with a user-friendly,non-invasive, and precise means for treating rhinorrhea and othersymptoms of rhinosinusitis by targeting only those specific neuralstructures associated with such conditions, notably postganglionicparasympathetic nerves innervating nasal mucosa, thereby disrupting theparasympathetic nerve supply and interrupting parasympathetic tone.Accordingly, such treatment is effective at treating rhinosinusitisconditions while greatly reducing the risk of causing lateral damage ordisruption to other nerve fibers, thereby reducing the likelihood ofunintended complications and side effects.

One aspect of the invention provides a device for treating a conditionwithin a nasal cavity of a patient. The device includes a multi-segmentend effector for delivering energy to one or more target sites withinthe nasal cavity of the patient. The multi-segment end effector includesa proximal segment that is spaced apart from a distal segment.

In some embodiments, the proximal segment comprises a first set offlexible support elements arranged in a first configuration and a firstset of electrodes provided by the first set of support elements andconfigured to deliver energy to tissue at a first target site. Thedistal segment comprises a second set of flexible support elementsarranged in a second configuration and a second set of electrodesprovided by the second set of support elements and configured to deliverenergy to tissue at a second target site. Each of the proximal anddistal segments is transformable between a retracted configuration andan expanded deployed configuration such that the first and second setsof flexible support elements are configured to position one or more ofthe respective first and second sets of electrodes at the first andsecond target sites when in the deployed configuration. When in theexpanded deployed configuration, the first set of support elementscomprises a first pair of struts, each comprising a loop shape andextending upward and a second pair of struts, each comprising a loopshape and extending downward. The second set of support elements, whenin the expanded deployed configuration, comprises a second set ofstruts, each comprising a loop shape extending outward to form anopen-ended circumferential shape. The first and second sets of supportelements comprise deformable composite wires. The composite wires mayinclude a shape memory material, such as nitinol, for example.

In some embodiments, the first and second sets of electrodes areconfigured to deliver radiofrequency (RF) energy to tissue at respectivetarget sites within the nasal cavity, wherein the respective targetsites are associated with parasympathetic nerve supply. For example, thefirst and second sets of electrodes may be configured to deliver RFenergy at a level sufficient to therapeutically modulate postganglionicparasympathetic nerves innervating nasal mucosa at an innervationpathway within the nasal cavity of the patient. The innervation pathwaymay include a microforamina of a palatine bone of the patient. Thecondition to be treated by the device may include, but is not limitedto, allergic rhinitis, non-allergic rhinitis, chronic rhinitis, acuterhinitis, chronic sinusitis, acute sinusitis, chronic rhinosinusitis,acute rhinosinusitis, and medical resistant rhinitis.

In some embodiments, the first segment of the multi-segment end effectorhas a first geometry to complement anatomy at a first location withinthe nasal cavity and the second segment of the multi-segment endeffector has a second geometry to complement anatomy at a secondlocation within the nasal cavity. Each of the first and second segmentsis transformable between a retracted configuration and an expandeddeployed configuration such that the first set of flexible supportelements of the first segment conforms to and complements a shape of afirst anatomical structure at the first location when the first segmentis in the deployed configuration and the second set of flexible supportelements of the second segment conforms to and complements a shape of asecond anatomical structure at the second location when the secondsegment is in the deployed configuration. The first and secondanatomical structures may include, but are not limited to, inferiorturbinate, middle turbinate, superior turbinate, inferior meatus, middlemeatus, superior meatus, pterygopalatine region, pterygopalatine fossa,sphenopalatine foramen, accessory sphenopalatine foramen(ae), andsphenopalatine micro-foramen(ae).

In some embodiments, the first segment of the multi-segment end effectoris configured in a deployed configuration to fit around at least aportion of a middle turbinate at an anterior position relative to themiddle turbinate and the second segment of the multi-segment endeffector is configured in a deployed configuration to contact aplurality of tissue locations in a cavity at a posterior positionrelative to the middle turbinate. For example, the first set of flexiblesupport elements of the first segment conforms to and complements ashape of a lateral attachment and posterior-inferior edge of the middleturbinate when the first segment is in the deployed configuration andthe second set of flexible support elements of the second segmentcontact a plurality of tissue locations in a cavity at a posteriorposition relative to the lateral attachment and posterior-inferior edgeof middle turbinate when the second segment is in the deployedconfiguration. Accordingly, when in the deployed configuration, thefirst and second segments are configured to position one or more ofrespective first and second sets of electrodes at one or more targetsites relative to the middle turbinate and the plurality of tissuelocations in the cavity behind the middle turbinate. In turn, the firstand second sets of electrodes are configured to deliver RF energy at alevel sufficient to therapeutically modulate postganglionicparasympathetic nerves innervating nasal mucosa at an innervationpathway within the nasal cavity of the patient.

Another aspect of the invention provides a device for treating acondition within a nasal cavity of a patient. The device comprises anend effector transformable between a retracted configuration and anexpanded deployed configuration, a shaft operably associated with theend effector, and a handle operably associated with the shaft. Thehandle includes a first mechanism for deployment of the end effectorfrom the retracted configuration to the expanded deployed configurationand a second mechanism, separate from the first mechanism, for controlof energy output by the end effector.

In some embodiments, the handle comprises an ergonomically-designed gripportion comprising a shape, size, and contour providing for ambidextroususe for both left and right handed use and conforming to handanthropometrics to allow for at least one of an overhand grip style andan underhand grip style during use in a procedure. The user input forthe first mechanism may be positioned on a top portion of the handleadjacent the grip portion and user input for the second mechanism ispositioned on side portions of the handle adjacent the grip portion. Theuser inputs for the first and second mechanisms may be positioned asufficient distance to one another to allow for simultaneous one-handedoperation of both user inputs during a procedure.

In some embodiments, the first mechanism comprises a rack and pinionassembly providing movement of the end effector between the retractedand deployed configurations in response to input from a user-operatedcontroller. The rack and pinion assembly may include a set of gears forreceiving input from the user-operated controller and converting theinput to linear motion of a rack member operably associated with atleast one of the shaft and the end effector. The rack and pinionassembly may include a gearing ratio sufficient to balance a strokelength and retraction and deployment forces, thereby improving controlover the deployment of the end effector.

In some embodiments, the user-operated controller comprises a slidermechanism operably associated with the rack and pinion rail assembly,wherein movement of the slider mechanism in a rearward direction towardsa proximal end of the handle results in transitioning of the endeffector to the deployed configuration and movement of the slidermechanism in a forward direction towards a distal end of the handleresults in transitioning of the end effector to the retractedconfiguration.

In some embodiments, the user-operated controller comprises a scrollwheel mechanism operably associated with the rack and pinion railassembly, wherein rotation of the wheel in a rearward direction towardsa proximal end of the handle results in transitioning of the endeffector to the deployed configuration and rotation of the wheel in aforward direction towards a distal end of the handle results intransitioning of the end effector to the retracted configuration.

In some embodiments, the second mechanism comprises a user-operatedcontroller configured to be actuated between an active position and aninactive position to thereby control delivery of energy from the endeffector. The user-operated controller may be multi-modal in that theuser-operated controller may be actuated between multiple positionsproviding different functions/modes. For example, upon a single userinput (i.e., single press of button associated within controller), thesecond mechanism may provide a baseline apposition/sensing checkfunction prior to modulation. Upon pressing and holding the controllerbutton for a pre-defined period of time, the energy output from the endeffector may be activated. Further, upon double-tapping the controllerbutton, energy output is deactivated.

In some embodiments, the handle may include a shape associated with thearchitecture of the end effector in the deployed configuration. Forexample, the handle may generally include a grip portion having a shapethat provides a user with a physical confirmation of an orientation ofportions of the end effector when in the deployed configuration. Forexample, the end effector may include a first segment that is spacedapart from a second segment, wherein each of the first and secondsegments is transformable between a retracted configuration and anexpanded deployed configuration. The handle comprises a grip portioncomprises a top, a bottom, sides, a proximal end, and a distal end,wherein at least one of the top, bottom, and sides of the grip portionof the handle is associated with architecture of at least one of thefirst and second segments of the end effector when in the deployedconfiguration. For example, the first segment may include a first set offlexible support elements and the second segment may include a secondset of flexible support elements. When in the deployed configuration,the first set of support elements may include a first pair of struts,each comprising a loop shape and extending upward and second pair ofstruts, each comprising a loop shape and extending downward. The top ofthe grip portion, for example, may be associated with the upwardlyextending first pair of struts and the bottom of the grip portion may beassociated with the downwardly extending second pair of struts. When inthe deployed configuration, the second set of support elements mayinclude a second set of struts, each comprising a loop shape extendingoutward to form an open-ended circumferential shape. The distal end ofthe grip portion may be associated with the outwardly extending secondset of struts.

In some embodiments, the handle and/or the shaft may include one or moremarkings that provide a user with a spatial orientation of the endeffector while the end effector is in a nasal cavity. For example, oneor more markings on the handle or shaft may provide a visual indicationof the orientation of one or more portions of the end effector,specifically an indication of the spatial orientation of one or both ofthe first and second segments in the deployed configurations. Themarkings may include any visual mark, such as text, symbols, andcolor-coding insignia. In some embodiments, multiple markings may beprovided to provide visual indication of one or more portions of thefirst and second segments when in deployed configurations. For example,a first marking on either or both of the handle and shaft may beassociated with the upwardly extending first pair of struts of the firstsegment of the end effector and a second marking may be associated withthe downwardly extending second pair of struts of the first segment ofthe end effector. As such, the first marking provides a user with avisual indication of the spatial orientation of the upwardly extendingfirst pair of struts and the second marking provides a user with avisual indication of the spatial orientation of the downwardly extendingsecond pair of struts while the first segment is in a nasal cavity inthe deployed configuration.

Another aspect of the invention provides a method for treating acondition within a nasal cavity of a patient. The method includesadvancing a device comprising a multi-segment end effector fordelivering energy to one or more target sites within the nasal cavity ofthe patient. The multi-segment end effector comprises a proximal segmentthat is spaced apart from a distal segment. The method further includesdelivering energy, via the proximal and distal segments, to tissue atthe one or more target sites.

In some embodiments, the proximal segment comprises a first set offlexible support elements arranged in a first configuration and a firstset of electrodes provided by the first set of support elements andconfigured to deliver energy to tissue at a first target site. Thedistal segment comprises a second set of flexible support elementsarranged in a second configuration and a second set of electrodesprovided by the second set of support elements and configured to deliverenergy to tissue at a second target site. Each of the proximal anddistal segments is transformable between a retracted configuration andan expanded deployed configuration such that the first and second setsof flexible support elements are configured to position one or more ofthe respective first and second sets of electrodes at the first andsecond target sites when in the deployed configuration. When in theexpanded deployed configuration, the first set of support elementscomprises a first pair of struts, each comprising a loop shape andextending upward and a second pair of struts, each comprising a loopshape and extending downward. The second set of support elements, whenin the expanded deployed configuration, comprises a second set ofstruts, each comprising a loop shape extending outward to form anopen-ended circumferential shape. The first and second sets of supportelements comprise deformable composite wires and may include a shapememory material, such as nitinol.

In some embodiments the method further includes deploying the proximaland distal segments of the multi-segment end effector at respectivefirst and second target sites to thereby position one or more of therespective first and second sets of electrodes at the first and secondtarget sites. The delivering of energy via the proximal and distalsegments comprises delivering radiofrequency (RF) energy, via one ormore of the respective first and second sets of electrodes, at a levelsufficient to therapeutically modulate postganglionic parasympatheticnerves innervating nasal mucosa at an innervation pathway within thenasal cavity of the patient.

In some embodiments, the first segment of the end effector has a firstgeometry to complement anatomy at a first location within the nasalcavity and the second segment has a second geometry to complementanatomy at a second location within the nasal cavity. Accordingly, themethod may include deploying the first and second segments at therespective first and second locations within the nasal cavity anddelivering energy, via the first and second segments, to tissue at theone or more target sites with respect to the first and second locations.

In some embodiments, the first set of flexible support elements of thefirst segment conforms to and complements a shape of a first anatomicalstructure at the first location when the first segment is in thedeployed configuration and the second set of flexible support elementsof the second segment conforms to and complements a shape of a secondanatomical structure at the second location when the second segment isin the deployed configuration. The first and second anatomicalstructures may include, but are not limited to, inferior turbinate,medial turbinate, superior turbinate, inferior meatus, middle meatus,superior meatus, and sphenopalatine foramen.

In some embodiments, the first segment of the end effector is configuredin a deployed configuration to fit around at least a portion of a middleturbinate at an anterior position relative to the middle turbinate andthe second segment of the end effector is configured in a deployedconfiguration to contact a plurality of tissue locations in a cavity ata posterior position relative to the middle turbinate. For example, thefirst set of flexible support elements of the first segment conforms toand complements a shape of a lateral attachment of the middle turbinateat the anterior position when the first segment is in the deployedconfiguration and the second set of flexible support elements of thesecond segment conforms to and complements a shape of at least a secondanatomical structure in the cavity posterior to the lateral attachmentof the middle turbinate when the second segment is in the deployedconfiguration. Accordingly, when in the deployed configuration, thefirst and second segments are configured to position one or more ofrespective first and second sets of electrodes at one or more targetsites relative to the middle turbinate and the plurality of tissuelocations in the cavity behind the middle turbinate. In turn, the firstand second sets of electrodes deliver RF energy at a level sufficient totherapeutically modulate postganglionic parasympathetic nervesinnervating nasal mucosa at an innervation pathway within the nasalcavity of the patient.

Another aspect of the invention provides a method for treating acondition within a nasal cavity of a patient. The method includesproviding a treatment device comprising an end effector transformablebetween a retracted configuration and an expanded deployedconfiguration, a shaft operably associated with the end effector, and ahandle operably associated with the shaft. The handle comprises a firstmechanism for deployment of the end effector from the retractedconfiguration to the expanded deployed configuration and a secondmechanism, separate from the first mechanism, for control of energyoutput by the end effector. The method includes advancing the endeffector to one or more target sites within the nasal cavity of thepatient, the end effector configured for delivering energy to one ormore target sites within the nasal cavity. The method further includesdeploying, via user input with the first mechanism on the handle, theend effector at the one or more target sites and delivering energy fromthe end effector, via user input with the second mechanism, to tissue atthe one or more target sites.

In some embodiments, the handle comprises a shape associated with thearchitecture of the end effector in the deployed configuration. Forexample, the handle may generally include a grip portion having a shapethat provides a user with a physical confirmation of an orientation ofportions of the end effector when in the deployed configuration.Accordingly, during advancement of the end effector to the one or moretarget sites within the nasal cavity, the method further includespositioning the end effector at the one or more target sites based, atleast in part, on orientation of the handle.

In some embodiments, the handle and/or the shaft may include one or moremarkings that provide a user with a spatial orientation of the endeffector while the end effector is in a nasal cavity. For example, oneor more markings on the handle or shaft may provide a visual indicationof the orientation of one or more portions of the end effector,specifically an indication of the spatial orientation of one or both ofthe first and second segments of the end effector in the deployedconfigurations. The markings may include any visual mark, such as text,symbols, and color-coding insignia. In some embodiments, multiplemarkings may be provided to provide visual indication of one or moreportions of the first and second segments when in deployedconfigurations. Accordingly, during advancement of the end effector tothe one or more target sites within the nasal cavity, the method furtherincludes positioning the end effector at the one or more target sitesbased, at least in part, on orientation of the handle or the shaft andthe one or more markings arranged about the handle or shaft.

Another aspect of the invention provides a device for treating acondition within a nasal cavity of a patient. The device includes amulti-segment end effector comprising at least a first retractable andexpandable segment comprising a micro-electrode array arranged about aplurality of struts. The plurality of struts have a bilateral geometryconforming to and accommodating an anatomical structure within the nasalcavity when the first segment is in an expanded state. In particular,when in the expanded state, the plurality of struts contact multiplelocations along multiple portions of the anatomical structure andelectrodes of the micro-electrode array are configured to emit energy ata level sufficient to create multiple micro-lesions in tissue of theanatomical structure that interrupt neural signals to mucus producingand/or mucosal engorgement elements.

In some embodiments, the bilateral geometry comprises at least firststrut that conforms to and accommodates a first side of the anatomicalstructure and at least a second strut that conforms to and accommodatesa second side of the anatomical structure when the first segment is inthe expanded state. When the first segment is in the expanded state, thefirst strut contacts multiple locations along the first side of theanatomical structure and a first set of electrodes of themicro-electrode array provided by the first strut is configured to emitenergy at a level sufficient to create multiple respective micro-lesionsin tissue along the first side of the anatomical structure. Similarly,when the first segment is in the expanded state, the second strutcontacts multiple locations along the second side of the anatomicalstructure and a second set of electrodes of the micro-electrode arrayprovided by the second strut are configured to emit energy at a levelsufficient to create multiple respective micro-lesions in tissue alongthe second side of the anatomical structure. The anatomical structuremay include, but is not limited to, an inferior turbinate, middleturbinate, superior turbinate, inferior meatus, middle meatus, superiormeatus, pterygopalatine region, pterygopalatine fossa, sphenopalatineforamen, accessory sphenopalatine foramen(ae), and sphenopalatinemicro-foramen(ae).

In some embodiments, each of the first and second struts has a loopshape and extends in an outward direction away from one another. Thefirst and second struts comprise deformable composite wires, thecomposite wires comprising shape memory material. Each strut may includemultiple electrodes of the electrode array positioned at separate anddiscrete portions of the strut. As such, when in the expanded state,each strut may position at least one associated electrode of themicro-electrode array into contact with tissue at a separate respectivelocation on a respective side of the anatomical structure for deliveryof energy thereto. The electrodes of the micro-electrode array areconfigured to be independently activated and controlled to therebydeliver energy independent of one another.

Another aspect of the invention provides a system for treating acondition within a nasal cavity of a patient. The system includes adevice comprising a multi-segment end effector for delivering energy toone or more target sites within the nasal cavity of the patient andfurther sensing one or more properties of the one or more target sites.The multi-segment end effector includes a proximal segment that isspaced apart from a distal segment, wherein each of the proximal anddistal segments has a specific geometry to complement anatomy at arespective location within the nasal cavity and associated with the oneor more target sites. The system further includes a console unitoperably associated with the device and configured to receive data fromthe device associated with the one or more properties of the one or moretarget sites and process data to provide information to an operatorrelated to the one or more target sites.

The console unit is configured to provide information associated with atleast one of: the identification and location of target and non-targetneural structures at the one or more target sites prior to therapeuticmodulation treatment thereof provided by at least one of the proximaland distal segments of the end effector; the identification and locationof target and non-target anatomical structures at the one or more targetsites prior to therapeutic modulation treatment thereof provided by atleast one of the proximal and distal segments of the end effector;real-time feedback associated with efficacy of therapeutic modulationtreatment on the one or more target neural and/or anatomic structuresduring therapeutic modulation treatment; and feedback associated withefficacy of therapeutic modulation treatment on the one or more targetneural and/or anatomic structures after therapeutic modulationtreatment.

In some embodiments, each of the proximal and distal segments of the endeffector comprises flexible struts and a plurality of elements providedby the struts.

For example, a first subset of the of the plurality of elements may beconfigured to deliver non-therapeutic stimulating energy to tissue atthe one or more target sites at a frequency for locating at least one oftarget neural structures, non-target neural structures, targetanatomical structures, and non-target anatomical structures. A secondsubset of the plurality of elements may be configured to senseproperties of at least one of the target neural structures, non-targetneural structures, target anatomical structures, and non-targetanatomical structures in response to the stimulating energy. Theproperties may include, but are not limited to, at least one of aphysiological properties, bioelectric properties, and thermalproperties. The bioelectric properties may include, but are not limitedto, at least one of complex impedance, resistance, reactance,capacitance, inductance, permittivity, conductivity, nerve firingvoltage, nerve firing current, depolarization, hyperpolarization,magnetic field, and induced electromotive force.

In some embodiments, the proximal segment of the end effector comprisesa first set of flexible struts arranged in a first configuration and thedistal segment of the end effector comprises a second set of flexiblestruts arranged in a second configuration. Each of the proximal anddistal segments may be transformable between a retracted configurationand an expanded deployed configuration such that the first set offlexible struts conforms to and complements a shape of a firstanatomical structure at a first location when the proximal segment is inthe deployed configuration and the second set of flexible strutsconforms to and complements a shape of a second anatomical structure ata second location when the distal segment is in the deployedconfiguration. The first and second anatomical structures may include,but are not limited to, an inferior turbinate, middle turbinate,superior turbinate, inferior meatus, middle meatus, superior meatus,pterygopalatine region, pterygopalatine fossa, sphenopalatine foramen,accessory sphenopalatine foramen(ae), and sphenopalatinemicro-foramen(ae).

The first set of flexible struts and the second set of flexible strutsmay be configured to position one or more of the respective plurality ofelements provided by each at respective one or more target sites when inthe deployed configurations. For example, when in the expanded deployedconfiguration, the first set of flexible struts may include a first pairof struts, each comprising a loop shape and extending upward and asecond pair of struts, each comprising a loop shape and extendingdownward. When in the expanded deployed configuration, the second set offlexible struts may include a second set of struts, each comprising aloop shape extending outward to form an open-ended circumferentialshape. As such, the first and second sets of flexible struts maygenerally include deformable composite wires, wherein the compositewires comprise shape memory material.

In some embodiments, the console unit is configured to detect and/or maplocations of at least one of the target neural structures, non-targetneural structures, target anatomical structures, and non-targetanatomical structures and control the delivery of therapeutic energyfrom at least one of the proximal and distal segments of the endeffector in a modulation pattern based on the locations of at least oneof the target neural structures, non-target neural structures, targetanatomical structures, and non-target anatomical structures. At leastsome of the elements provided by at least one of the proximal and distalsegments are configured to deliver energy based on the modulationpattern at a level sufficient to therapeutically modulate one or morenerves associated with the locations of the target neural and/or targetanatomical structures while avoiding locations of the non-target neuraland/or target anatomical structures. The at least some of the elementsare configured to delivery energy based on the modulation pattern at alevel insufficient to therapeutically modulate the non-target neuraland/or non-target anatomical structures.

In some embodiments, the console unit comprises a controller configuredto selectively control energy output from elements of the proximaland/or distal segments of the end effector, wherein some of the elementsare configured to be independently activated and controlled to therebydeliver energy independent of one another. The controller may beconfigured to adjust energy output from elements of the proximal and/ordistal segments of the end effector based, at least in part, on thereal-time feedback associated with the effectiveness of therapeuticmodulation treatment on the one or more target anatomic and/or neuralstructures during therapeutic modulation thereof.

Another aspect of the invention provides a method for treating acondition within a nasal cavity of a patient. The method includesproviding a treatment device comprising a multi-segment end effector,including a proximal segment that is spaced apart from a distal segment,and a visual marker. The method further includes advancing, under imageguidance, the proximal segment and the distal segment through a nasalcavity of a patient and past a middle turbinate and deploying the distalsegment from a retracted configuration to an expanded configuration. Theproximal segment is then aligned, under the image guidance and withreference to the visual marker, with respect to the middle turbinate.Upon alignment, the method includes deploying the proximal segmentaround the middle turbinate. The method further includes advancing thedeployed proximal segment toward the middle turbinate to establishcontact and secure the proximal segment to the middle turbinate.

The deployed proximal segment has a geometry to complement a shape ofthe middle turbinate and/or a lateral attachment of the middleturbinate, thereby ensuring that the deployed proximal segment issecured to the middle turbinate and/or lateral attachment of the middleturbinate. For example, in some embodiments, the proximal segmentcomprises a set of flexible support elements that conform to andcomplement a shape of the middle turbinate and/or the lateral attachmentof the middle turbinate when the proximal segment is in the deployedexpanded configuration.

The method may further include delivering energy, via the proximalsegment, to the middle turbinate and/or a lateral attachment of themiddle turbinate and/or a lateral wall of the nasal cavity to treat acondition. The condition may include, but is not limited to, allergicrhinitis, non-allergic rhinitis, chronic rhinitis, acute rhinitis,chronic sinusitis, acute sinusitis, chronic rhinosinusitis, acuterhinosinusitis, and medical resistant rhinitis, and a combinationthereof. In some embodiments, delivering energy from the proximalsegment includes delivering radiofrequency (RF) energy, via one or moreelectrodes provided by the proximal segment, to tissue of the lateralwall around the middle turbinate at one or more target sites, whereinthe one or more target sites are associated with one or more neurogenicpathways. In some embodiments, RF energy is delivered, via the one ormore electrodes provided by the proximal segment, at a level sufficientto disrupt one or more neurogenic pathways associated with thecondition, such as neurogenic pathways that result in rhinorrhea and/orcongestion. In other embodiments, RF energy is delivered, via the one ormore electrodes provided by the proximal segment, at a level sufficientto therapeutically modulate one or more postganglionic parasympatheticnerves innervating nasal mucosa at a neurogenic pathway.

In some embodiments, the visual marker is provided by a shaft operablyassociated with the multi-segment end effector. The visual markerprovides a visual indication of a spatial orientation of one or moreportions of the proximal segment. The visual marker may include, forexample, text, symbols, color-coding insignia, or the like. In someembodiments, the step of aligning the proximal segment with respect tothe middle turbinate comprises positioning, under the image guidance,the shaft and associated visual marker relative to the middle turbinate,and/or a posterior lateral attachment of the middle turbinate and/or alateral nasal wall.

Another aspect of the invention provides a system for treating acondition within a nasal cavity of a patient. The system includes atreatment device and an image guidance assembly for providing visualdepictions of one or more portions of the treatment device to aid a user(i.e., surgeon or other medical professional) in carrying out aprocedure for treating the condition with the nasal cavity of thepatient.

The treatment device includes a multi-segment end effector comprisingproximal segment that is spaced apart from a distal segment, a shaftoperably associated with the multi-segment end effector, and a handleoperably associated with the multi-segment end effector and the shaft.The shaft includes one or more visual markers for providing a user witha visual indication, under the image guidance, of a spatial orientationof at least the proximal segment while the multi-segment end effector iswithin in a nasal cavity of a patient. The handle includes a controllermechanism for providing independent, controlled deployment of each ofthe proximal and distal segments from a retracted configuration to anexpanded configuration within the nasal cavity. The image guidanceassembly provides a visual depiction of at least the shaft and visualmarker relative to surrounding anatomy of the nasal cavity to therebyassist a user in deployment and positioning of at least the proximalsegment within the nasal cavity.

In some embodiments, at least one visual marker is associated with aspatial orientation of a portion of the proximal segment when theproximal segment is in an expanded configuration. The visual marker mayinclude, for example, text, symbols, color-coding insignia, or the like.

The proximal segment may include a geometry to complement a shape of themiddle turbinate and/or a lateral attachment of the middle turbinatewhen in the expanded configuration, thereby ensuring that the deployedproximal segment may establish sufficient contact with, and be securelyengaged to, the middle turbinate and/or the lateral attachment of themiddle turbinate. For example, the proximal segment may include a set offlexible support elements that conform to and complement a shape of themiddle turbinate and/or the lateral attachment of the middle turbinatewhen the proximal segment is in the expanded configuration. The distalsegment may include a geometry to complement a shape of anotheranatomical structure within the nasal cavity when in an expandedconfiguration.

In some embodiments, the controller mechanism includes a rack and pinionassembly providing movement of the at least one of the proximal anddistal segments between the retracted configuration and expandedconfiguration in response to user input from an associated user-operatedcontroller. The rack and pinion assembly may include, for example, a setof gears for receiving user input from the user-operated controller andconverting the user input to linear motion of a rack member operablyassociated with the multi-segment end effector.

In some embodiments, the controller mechanism may further include adetent feature positioned relative to the proximal and distal segmentsand configured to provide active feedback to a user indicative ofdeployment of at least one of the proximal and distal segments. Theactive feedback may be in the form haptic feedback provided by thecontroller mechanism. For example, the haptic feedback may include anincrease or decrease in resistance associated with user input with thecontroller mechanism for corresponding movement of the at least one ofthe proximal and distal segments between retracted and expandedconfigurations, and/or configurations therebetween (i.e., a plurality ofconfigurations between a fully retracted configuration and a fullyexpanded configuration).

In some embodiments, the controller mechanism may further include afriction-based feature configured to provide stable movement of at leastone of the proximal and distal segments between the retracted andexpanded configurations and further provide active feedback to a userindicative of deployment of at least one of the proximal and distalsegments. The friction-based feature may include a lock mechanismproviding constant friction between one or more portions of the rack andpinion assembly sufficient to maintain a position of at least one of theproximal and distal segments during deployment thereof. For example, theconstant friction may be sufficient to hold either of the proximal ordistal segments in a certain position as the segment transitions betweenretracted and expanded configurations regardless of whether the usermaintains contact with the user-operated controller. In other words, auser does not need to maintain contact with the user-operated controllerin order to ensure that the proximal or distal segment holds a certainposition during deployment thereof. Rather, a user can simply interactwith the user-operated controller to transition one of the proximal anddistal segments to a desired configuration and the constant frictionprovided by the locking mechanism is sufficient to maintain theconfiguration of proximal or distal segment in the event that the usergoes hands free (i.e., removes any contact with the user-operatedcontroller). The constant friction is of a level sufficient to preventundesired movement of the proximal or distal segments (i.e., unintendedcollapsing or expanding), while still allowing for a user to overcomesuch friction to move the proximal or distal segment to a desiredconfiguration upon user input with the user-operated controller.

In some embodiments, the user-operated controller includes a slidermechanism operably associated with the rack and pinion rail assembly,wherein movement of the slider mechanism in a first direction results intransitioning of at least one of the proximal and distal segments to anexpanded configuration and movement of the slider mechanism in a secondopposite direction results in transitioning of at least one of theproximal and distal segments to the retracted configuration.

In other embodiments, the user-operated controller includes a scrollwheel mechanism operably associated with the rack and pinion railassembly, wherein rotation of the wheel in a first direction results intransitioning of at least one of the proximal and distal segments to anexpanded configuration and rotation of the wheel in a second oppositedirection results in transitioning of at least one of the proximal anddistal segments to the retracted configuration.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B are diagrammatic illustrations of a therapeuticneuromodulation system for treating a condition within a nasal cavityusing a handheld device according to some embodiments of the presentdisclosure.

FIG. 2 is a diagrammatic illustration of the console coupled to thehandheld neuromodulation device consistent with the present disclosure,further illustrating a multi-segment end effector of the handheld devicefor delivering energy, via proximal and distal segments, to tissue atthe one or more target sites within the nasal cavity.

FIG. 3A is a cut-away side view illustrating the anatomy of a lateralnasal wall.

FIG. 3B is an enlarged side view of the nerves of the lateral nasal wallof FIG. 1A.

FIG. 3C is a front view of a left palatine bone illustrating geometry ofmicroforamina in the left palatine bone.

FIG. 4 is a side view of one embodiment of a handheld device forproviding therapeutic nasal neuromodulation consistent with the presentdisclosure.

FIG. 5A is an enlarged, perspective view of the multi-segment endeffector illustrating the first (proximal) segment and second (distal)segment.

FIG. 5B is an exploded, perspective view of the multi-segment endeffector.

FIG. 5C is an enlarged, top view of the multi-segment end effector.

FIG. 5D is an enlarged, side view of the multi-segment end effector.

FIG. 5E is an enlarged, front (proximal facing) view of the first(proximal) segment of the multi-segment end effector.

FIG. 5F is an enlarged, front (proximal facing) view of the second(distal) segment of the multi-segment end effector.

FIG. 6 is a perspective view, partly in section, of a portion of asupport element illustrating an exposed conductive wire serving as anenergy delivery element or electrode element.

FIG. 7 is a cross-sectional view of a portion of the shaft of thehandheld device taken along lines 7-7 of FIG. 4.

FIG. 8 is a side view of the handle of the handheld device.

FIG. 9 is a side view of the handle illustrating internal componentsenclosed within.

FIG. 10 is a side view of the handle illustrating multiple markings on aportion of the handle for providing a user with a spatial orientation ofthe end effector while the end effector is in a nasal cavity.

FIG. 11 is a perspective view of the shaft illustrating multiplemarkings on a distal portion thereof for providing a user with a spatialorientation of the end effector while the end effector is in a nasalcavity.

FIG. 12 is a partial cut-away side views illustrating one approach fordelivering an end effector a target site within a nasal region inaccordance with embodiments of the present disclosure.

FIG. 13 is a flow diagram illustrating one embodiment of a method fortreating a condition within a nasal cavity of a patient.

FIG. 14 is a flow diagram illustrating another embodiment of a methodfor treating a condition within a nasal cavity of a patient.

FIG. 15 is a flow diagram illustrating another embodiment of a methodfor treating a condition within a nasal cavity of a patient.

DETAILED DESCRIPTION

There are various conditions related to the nasal cavity which mayimpact breathing and other functions of the nose. One of the more commonconditions is rhinitis, which is defined as inflammation of themembranes lining the nose. The symptoms of rhinitis include nasalblockage, obstruction, congestion, nasal discharge (e.g., rhinorrheaand/or posterior nasal drip), facial pain, facial pressure, and/orreduction or complete loss of smell and/or taste. Sinusitis is anothercommon condition, which involves an inflammation or swelling of thetissue lining the sinuses, which can lead to subsequent. Rhinitis andsinusitis are frequently associated with one another, as sinusitis isoften preceded by rhinitis. Accordingly, the term rhinosinusitis isoften used to describe both conditions.

Depending on the duration and type of systems, rhinosinusitis can fallwithin different subtypes, including allergic rhinitis, non-allergicrhinitis, chronic rhinitis, acute rhinitis, recurrent rhinitis, chronicsinusitis, acute sinusitis, recurrent sinusitis, and medical resistantrhinitis and/or sinusitis, in addition to combinations of one or more ofthe preceding conditions. It should be noted that an acuterhinosinusitis condition is one in which symptoms last for less thantwelve weeks, whereas a chronic rhinosinusitis condition refers tosymptoms lasting longer than twelve weeks.

A recurrent rhinosinusitis condition refers to four or more episodes ofan acute rhinosinusitis condition within a twelve-month period, withresolution of symptoms between each episode. There are numerousenvironmental and biological causes of rhinosinusitis. Non-allergicrhinosinusitis, for example, can be caused by environmental irritants,medications, foods, hormonal changes, and/or nasal septum deviation.Triggers of allergic rhinitis can include exposure to seasonalallergens, perennial allergens that occur any time of year, and/oroccupational allergens. Accordingly, rhinosinusitis affects millions ofpeople and is a leading cause for patients to seek medical care.

The present invention provides systems and methods for therapeuticallymodulating nerves in a nasal region of a patient for the effectivetreatment of rhinosinusitis conditions. Particularly, aspects of thepresent invention include systems and methods for performing anaccurate, minimally invasive, and localized application of energy to oneor more target sites within the nasal cavity to disrupt theparasympathetic motor sensory function associated with rhinosinusitisconditions, without causing collateral damage or disruption to otherneural structures.

It should be noted that, although many of the embodiments are describedwith respect to devices, systems, and methods for therapeuticallymodulating nerves in the nasal region for the treatment of rhinitis,other applications and other embodiments in addition to those describedherein are within the scope of the present disclosure. For example, atleast some embodiments of the present disclosure may be useful for thetreatment of other indications, such as the treatment of chronicsinusitis and epistaxis. In particular, the embodiments described hereinmay be configured to treat allergic rhinitis, non-allergic rhinitis,chronic rhinitis, acute rhinitis, chronic sinusitis, acute sinusitis,chronic rhinosinusitis, acute rhinosinusitis, and/or medical resistantrhinitis.

FIGS. 1A and 1B are diagrammatic illustrations of a therapeuticneuromodulation system 100 for treating a condition within a nasalcavity using a handheld device 102 according to some embodiments of thepresent disclosure. The system 100 generally includes a neuromodulationdevice 102 and a neuromodulation console 104 to which the device 102 isto be connected. FIG. 2 is a diagrammatic illustration of the console104 coupled to the handheld neuromodulation device 102. As illustrated,the neuromodulation device 102 is a handheld device, which includes aretractable and expandable multi-segment end effector 114, a shaft 116operably associated with the end effector 114 and a handle 118 operablyassociated with the shaft 116. The end effector 114 is configured to beadvanced into the nasal cavity of a patient 12 and positioned at alocation associated with one or more target sites to undergo therapeuticneuromodulation treatment. It should be noted that the terms “endeffector” and “therapeutic assembly” may be used interchangeablythroughout this disclosure.

For example, a surgeon or other medical professional performing aprocedure can utilize the handle 118 to manipulate and advance the shaft116 within the nasal cavity, wherein the shaft 116 is configured tolocate at least a distal portion thereof intraluminally at a treatmentor target site within a nasal region. The one or more target sites maygenerally be associated with postganglionic parasympathetic fibers thatinnervate the nasal mucosa. The target site may be a region, volume, orarea in which the target nerves are located and may differ in size andshape depending upon the anatomy of the patient. Once positioned, theend effector 114 may be deployed and subsequently deliver energy to theone or more target sites to thereby therapeutically modulating nerves ofinterest, particularly nerves associated with a rhinosinusitis conditionso as to treat such condition. For example, the end effector 114 mayinclude at least one energy delivery element, such as an electrode,configured to therapeutically modulate the postganglionicparasympathetic nerves. For example, one or more electrodes may beprovided by one or more portions of the end-effector 114, wherein theelectrodes may be configured to apply electromagnetic neuromodulationenergy (e.g., radiofrequency (RF) energy) to target sites. In otherembodiments, the end effector 114 may include other energy deliveryelements configured to provide therapeutic neuromodulation using variousother modalities, such as cryotherapeutic cooling, ultrasound energy(e.g., high intensity focused ultrasound (“HIFU”) energy), microwaveenergy (e.g., via a microwave antenna), direct heating, high and/or lowpower laser energy, mechanical vibration, and/or optical power.

In some embodiments, the end effector 114 may include one or moresensors (not shown), such as one or more temperature sensors (e.g.,thermocouples, thermistors, etc.), impedance sensors, and/or othersensors. The sensors and/or the electrodes may be connected to one ormore wires extending through the shaft 116 and configured to transmitsignals to and from the sensors and/or convey energy to the electrodes.

As shown, the device 102 is operatively coupled to the console 104 via awired connection, such as cable 120. It should be noted, however, thatthe device 102 and console 104 may be operatively coupled to one anothervia a wireless connection. The console 104 is configured to providevarious functions for the neuromodulation device 102, which may include,but is not limited to, controlling, monitoring, supplying, and/orotherwise supporting operation of the neuromodulation device 102. Forexample, when the neuromodulation device 102 is configured forelectrode-based, heat-element-based, and/or transducer-based treatment,the console 104 may include an energy generator 106 configured togenerate RF energy (e.g., monopolar, bipolar, or multi-polar RF energy),pulsed electrical energy, microwave energy, optical energy, ultrasoundenergy (e.g., intraluminally-delivered ultrasound and/or HIFU), directheat energy, radiation (e.g., infrared, visible, and/or gammaradiation), and/or another suitable type of energy.

In some embodiments, the console 104 may include a controller 107communicatively coupled to the neuromodulation device 102. However, inthe embodiments described herein, the controller 107 may generally becarried by and provided within the handle 118 of the neuromodulationdevice 102. The controller 107 is configured to initiate, terminate,and/or adjust operation of one or more electrodes provided by the endeffector 114 directly and/or via the console 104. For example, thecontroller 107 can be configured to execute an automated controlalgorithm and/or to receive control instructions from an operator (e.g.,surgeon or other medical professional or clinician). For example, thecontroller 107 and/or other components of the console 104 (e.g.,processors, memory, etc.) can include a computer-readable mediumcarrying instructions, which when executed by the controller 107, causesthe device 102 to perform certain functions (e.g., apply energy in aspecific manner, detect impedance, detect temperature, detect nervelocations or anatomical structures, etc.). A memory includes one or moreof various hardware devices for volatile and non-volatile storage, andcan include both read-only and writable memory. For example, a memorycan comprise random access memory (RAM), CPU registers, read-only memory(ROM), and writable non-volatile memory, such as flash memory, harddrives, floppy disks, CDs, DVDs, magnetic storage devices, tape drives,device buffers, and so forth. A memory is not a propagating signaldivorced from underlying hardware; a memory is thus non-transitory.

The console 104 may further be configured to provide feedback to anoperator before, during, and/or after a treatment procedure viaevaluation/feedback algorithms 110. For example, the evaluation/feedbackalgorithms 110 can be configured to provide information associated withthe temperature of the tissue at the treatment site, the location ofnerves at the treatment site, and/or the effect of the therapeuticneuromodulation on the nerves at the treatment site. In certainembodiments, the evaluation/feedback algorithm 110 can include featuresto confirm efficacy of the treatment and/or enhance the desiredperformance of the system 100. For example, the evaluation/feedbackalgorithm 110, in conjunction with the controller 107, can be configuredto monitor temperature at the treatment site during therapy andautomatically shut off the energy delivery when the temperature reachesa predetermined maximum (e.g., when applying RF energy) or predeterminedminimum (e.g., when applying cryotherapy). In other embodiments, theevaluation/feedback algorithm 110, in conjunction with the controller107, can be configured to automatically terminate treatment after apredetermined maximum time, a predetermined maximum impedance rise ofthe targeted tissue (i.e., in comparison to a baseline impedancemeasurement), a predetermined maximum impedance of the targeted tissue),and/or other threshold values for biomarkers associated with autonomicfunction. This and other information associated with the operation ofthe system 100 can be communicated to the operator via a graphical userinterface (GUI) 112 provided via a display on the console 104 and/or aseparate display (not shown) communicatively coupled to the console 104,such as a tablet or monitor. The GUI 112 may generally provideoperational instructions for the procedure, such as directing theoperator to select which nasal cavity to treat, indicating when thedevice 102 is primed and ready to perform treatment, and furtherproviding status of therapy during the procedure, including indicatingwhen the treatment is complete.

For example, in some embodiments, the end effector 114 and/or otherportions of the system 100 can be configured to detect variousparameters of the heterogeneous tissue at the target site to determinethe anatomy at the target site (e.g., tissue types, tissue locations,vasculature, bone structures, foramen, sinuses, etc.), locate nervesand/or other structures, and allow for neural mapping. For example, theend effector 114 may be configured to detect impedance, dielectricproperties, temperature, and/or other properties that indicate thepresence of neural fibers in the target region. As shown in FIG. 1, theconsole 104 may further include a monitoring system 108 configured toreceive detected electrical and/or thermal measurements of tissue at thetarget site taken by the end effector 114, specifically sensed byappropriate sensors (e.g., temperature sensors and/or impedancesensors), and process this information to identify the presence ofnerves, the location of nerves, and/or neural activity at the targetsite. The nerve monitoring system 108 can be operably coupled to theelectrodes and/or other features of the end effector 102 via signalwires (e.g., copper wires) that extend through the cable 120 and throughthe length of the shaft 116. In other embodiments, the end effector 114can be communicatively coupled to the nerve monitoring system 108 usingother suitable communication means.

The nerve monitoring system 108 can determine neural locations andactivity before therapeutic neuromodulation to determine precisetreatment regions corresponding to the positions of the desired nerves,during treatment to determine the effect of the therapeuticneuromodulation, and/or after treatment to evaluate whether thetherapeutic neuromodulation treated the target nerves to a desireddegree. This information can be used to make various determinationsrelated to the nerves proximate to the target site, such as whether thetarget site is suitable for neuromodulation. In addition, the nervemonitoring system 108 can also compare the detected neural locationsand/or activity before and after therapeutic neuromodulation, andcompare the change in neural activity to a predetermined threshold toassess whether the application of therapeutic neuromodulation waseffective across the treatment site. For example, the nerve monitoringsystem 108 can further determine electroneurogram (ENG) signals based onrecordings of electrical activity of neurons taken by the end effector114 before and after therapeutic neuromodulation. Statisticallymeaningful (e.g., measurable or noticeable) decreases in the ENGsignal(s) taken after neuromodulation can serve as an indicator that thenerves were sufficiently ablated. Additional features and functions ofthe nerve monitoring system 108, as well as other functions of thevarious components of the console 104, including the evaluation/feedbackalgorithms 110 for providing real-time feedback capabilities forensuring optimal therapy for a given treatment is administered, aredescribed in at least U.S. Publication No. 2016/0331459 and U.S.Publication No. 2018/0133460, the contents of each of which areincorporated by reference herein in their entireties.

As will be described in greater detail herein, the neuromodulationdevice 102 provides access to target sites deep within the nasal region,such as at the immediate entrance of parasympathetic fibers into thenasal cavity to therapeutically modulate autonomic activity within thenasal cavity. In certain embodiments, for example, the neuromodulationdevice 102 can position the end effector 114 into contact with targetsites within nasal cavity associated with postganglionic parasympatheticfibers that innervate the nasal mucosa.

FIG. 3A is a cut-away side view illustrating the anatomy of a lateralnasal wall and FIG. 3B is an enlarged side view of the nerves of thelateral nasal wall of FIG. 1A. The sphenopalatine foramen (SPF) is anopening or conduit defined by the palatine bone and the sphenoid bonethrough which the sphenopalatine vessels and the posterior superiornasal nerves travel into the nasal cavity. More specifically, theorbital and sphenoidal processes of the perpendicular plate of thepalatine bone define the sphenopalatine notch, which is converted intothe SPF by the articulation with the surface of the body of the sphenoidbone.

The location of the SPF is highly variable within the posterior regionof the lateral nasal cavity, which makes it difficult to visually locatethe SPF. Typically, the SPF is located in the middle meatus (MM).However, anatomical variations also result in the SPF being located inthe superior meatus (SM) or at the transition of the superior and middlemeatuses. In certain individuals, for example, the inferior border ofthe SPF has been measured at about 19 mm above the horizontal plate ofthe palatine bone (i.e., the nasal sill), which is about 13 mm above thehorizontal lamina of the inferior turbinate (IT) and the averagedistance from the nasal sill to the SPF is about 64.4 mm, resulting inan angle of approach from the nasal sill to the SPA of about 11.4°.However, studies to measure the precise location of the SPF are oflimited practical application due to the wide variation of its location.

The anatomical variations of the SPF are expected to correspond toalterations of the autonomic and vascular pathways traversing into thenasal cavity. In general, it is thought that the posterior nasal nerves(also referred to as lateral posterior superior nasal nerves) branchfrom the pterygopalatine ganglion (PPG), which is also referred to asthe sphenopalatine ganglion, through the SPF to enter the lateral nasalwall of the nasal cavity, and the sphenopalatine artery passes from thepterygopalatine fossa through the SPF on the lateral nasal wall. Thesphenopalatine artery branches into two main portions: the posteriorlateral nasal branch and the posterior septal branch. The main branch ofthe posterior lateral nasal artery travels inferiorly into the inferiorturbinate IT (e.g., between about 1.0 mm and 1.5 mm from the posteriortip of the inferior turbinate IT), while another branch enters themiddle turbinate MT and branches anteriorly and posteriorly.

Beyond the SPF, studies have shown that over 30% of human patients haveone or more accessory foramen that also carries arteries and nerves intothe nasal cavity. The accessory foramen are typically smaller than theSPF and positioned inferior to the SPF. For example, there can be one,two, three or more branches of the posterior nasal artery and posteriornasal nerves that extend through corresponding accessory foramen. Thevariability in location, size, and quantity associated with theaccessory foramen and the associated branching arteries and nerves thattravel through the accessory foramen gives rise to a great deal ofuncertainty regarding the positions of the vasculature and nerves of thesphenopalatine region. Furthermore, the natural anatomy extending fromthe SPF often includes deep inferior and/or superior grooves that carryneural and arterial pathways, which make it difficult to locate arterialand neural branches. For example the grooves can extend more than 5 mmlong, more than 2 mm wide, and more than 1 mm deep, thereby creating apath significant enough to carry both arteries and nerves. Thevariations caused by the grooves and the accessory foramen in thesphenopalatine region make locating and accessing the arteries andnerves (positioned posterior to the arteries) extremely difficult forsurgeons.

Recent microanatomic dissection of the pterygopalatine fossa (PPF) havefurther evidenced the highly variable anatomy of the region surroundingthe SPF, showing that a multiplicity of efferent rami that project fromthe pterygopalatine ganglion (PPG) to innervate the orbit and nasalmucosa via numerous groups of small nerve fascicles, rather than anindividual postganglionic autonomic nerves (e.g., the posterior nasalnerve). Studies have shown that at least 87% of humans havemicroforamina and micro rami in the palatine bone.

FIG. 3C, for example, is a front view of a left palatine boneillustrating geometry of microforamina and micro rami in a left palatinebone. In FIG. 3C, the solid regions represent nerves traversing directlythrough the palatine bone, and the open circles represent nerves thatwere associated with distinct microforamina. As such, FIG. 3Cillustrates that a medial portion of the palatine bone can include atleast 25 accessory posterolateral nerves.

The respiratory portion of the nasal cavity mucosa is composed of a typeof ciliated pseudostratified columnar epithelium with a basementmembrane. Nasal secretions (e.g., mucus) are secreted by goblet cells,submucosal glands, and transudate from plasma. Nasal seromucous glandsand blood vessels are highly regulated by parasympathetic innervationderiving from the vidian and other nerves. Parasympathetic (cholinergic)stimulation through acetylcholine and vasoactive intestinal peptidegenerally results in mucus production. Accordingly, the parasympatheticinnervation of the mucosa is primarily responsible submucosal glandactivation/hyper activation, venous engorgement (e.g., congestion), andincreased blood flow to the blood vessels lining the nose. Accordingly,severing or modulating the parasympathetic pathways that innervate themucosa are expected to reduce or eliminate the hyper activation of thesubmucosal glands and engorgement of vessels that cause symptomsassociated with rhinosinusitis and other indications.

As previously described herein, postganglionic parasympathetic fibersthat innervate the nasal mucosa (i.e., posterior superior nasal nerves)were thought to travel exclusively through the SPF as a sphenopalatineneurovascular bundle. The posterior nasal nerves are branches of themaxillary nerve that innervate the nasal cavity via a number of smallermedial and lateral branches extending through the mucosa of the superiorand middle turbinates ST, MT (i.e., nasal conchae) and to the nasalseptum. The nasopalatine nerve is generally the largest of the medialposterior superior nasal nerves, and it passes anteroinferiorly in agroove on the vomer to the floor of the nasal cavity. From here, thenasopalatine nerve passes through the incisive fossa of the hard palateand communicates with the greater palatine nerve to supply the mucosa ofthe hard palate. The posterior superior nasal nerves pass through thepterygopalatine ganglion PPG without synapsing and onto the maxillarynerve via its ganglionic branches.

Based on the understanding that the posterior nasal nerves exclusivelytraverse the SPF to innervate the nasal mucosa, surgeries have beenperformed to selectively sever the posterior nasal nerve as it exits theSPF. However, as discussed above, the sinonasal parasympathetic pathwayactually comprises individual rami project from the pterygopalatineganglion (PPG) to innervate the nasal mucosa via multiple small nervefascicles (i.e., accessory posterolateral nerves), not a single branchextending through the SPF. These rami are transmitted through multiplefissures, accessory foramina, and microforamina throughout the palatinebone and may demonstrate anastomotic loops with both the SPF and otheraccessory nerves. Thus, if only the parasympathetic nerves traversingthe SPF were severed, almost all patients (e.g., 90% of patients ormore) would retain intact accessory secretomotor fibers to theposterolateral mucosa, which would result in the persistence of symptomsthe neurectomy was meant to alieve. Accordingly, embodiments of thepresent disclosure are configured to therapeutically modulate nerves atprecise and focused treatment sites corresponding to the sites of ramiextending through fissures, accessory foramina, and microforaminathroughout the palatine bone (e.g., target region T shown in FIG. 3B).In certain embodiments, the targeted nerves are postganglionicparasympathetic nerves that go on to innervate the nasal mucosa. Thisselective neural treatment is also expected to decrease the rate ofpostoperative nasal crusting and dryness because it allows a clinicianto titrate the degree of anterior denervation through judicious sparingof the rami orbitonasal. Furthermore, embodiments of the presentdisclosure are also expected to maintain at least some sympathetic toneby preserving a portion of the sympathetic contributions from the deeppetrosal nerve and internal maxillary periarterial plexus, leading toimproved outcomes with respect to nasal obstruction. In addition,embodiments of the present disclosure are configured to target amultitude of parasympathetic neural entry locations (e.g., accessoryforamen, fissures, and microforamina) to the nasal region to provide fora complete resection of all anastomotic loops, thereby reducing the rateof long-term re-innervation.

FIG. 4 is a side view of one embodiment of a handheld device 102 forproviding therapeutic nasal neuromodulation consistent with the presentdisclosure. As illustrated, the device 102 includes a multi-segment endeffector 114 transformable between a retracted configuration and anexpanded deployed configuration, a shaft 116 operably associated withthe end effector 114, and a handle 118 operably associated with theshaft 116. The multi-segment end effector 114 includes at least a firstsegment 122 and a second segment 124 spaced apart from one another. Thefirst segment 122 is generally positioned closer to a distal end of theshaft 116, and is thus sometimes referred to herein as the proximalsegment 122, while the second segment 124 is generally positionedfurther from the distal end of the shaft 116 and is thus sometimesreferred to herein as the distal segment 124. Each of the first andsecond segments 122 and 124 is transformable between a retractedconfiguration, which includes a low-profile delivery state to facilitateintraluminal delivery of the end effector 114 to a treatment site withinthe nasal region, and a deployed configuration, which includes anexpanded state, as shown in FIG. 4 and further illustrated in FIGS.5A-5F. The handle 118 includes at least a first mechanism 126 fordeployment of the multi-segment end effector 114, notably the first andsecond segments 122, 124, from the retracted configuration to thedeployed configuration and a second mechanism 128, separate from thefirst mechanism 124, for control of energy output by either of the firstand second segments 122, 124 of the end effector 114, specificallyelectrodes or other energy elements provided by first and/or secondsegments 122, 124. The handheld device 102 may further include anauxiliary line 121, which may provide a fluid connection between a fluidsource, for example, and the shaft 116 such that fluid may be providedto a target site via the distal end of the shaft 116. In someembodiments, the auxiliary line 121 may provide a connection between avacuum source and the shaft 116, such that the device 102 may includesuction capabilities (via the distal end of the shaft 116).

FIGS. 5A, 5B, 5C, 5D, 5E, and 5F are enlarged views of the multi-segmentend effector 114, illustrating various views of the first and secondsegments 122, 124 in greater detail. FIG. 5A is an enlarged, perspectiveview of the multi-segment end effector 114. FIG. 5B is an exploded,perspective view of the multi-segment end effector 114. FIGS. 5C and 5Dare enlarged, top and side views, respectively, of the multi-segment endeffector 114. FIG. 5E is an enlarged, front (proximal facing) view ofthe first segment 122 of the multi-segment end effector 114. FIG. 5F isan enlarged, front (proximal facing) view of the second segment 124 ofthe multi-segment end effector 114.

As illustrated, the first segment 122 includes at least a first set offlexible support elements, generally in the form of wires, arranged in afirst configuration, and the second segment 124 includes a second set offlexible support elements, also in the form of wires, arranged in asecond configuration. The first and second sets of flexible supportelements include composite wires having conductive and elasticproperties. For example, in some embodiments, the composite wiresinclude a shape memory material, such as nitinol. The flexible supportelements may further include a highly lubricious coating, which mayallow for desirable electrical insulation properties as well asdesirable low friction surface finish. Each of the first and secondsegments 122, 124 is transformable between a retracted configuration andan expanded deployed configuration such that the first and second setsof flexible support elements are configured to position one or moreelectrodes provided on the respective segments (see electrodes 136 inFIGS. 5E and 5F) into contact with one or more target sites when in thedeployed configuration.

As shown, when in the expanded deployed configuration, the first set ofsupport elements of the first segment 122 includes at least a first pairof struts 130 a, 130 b, each comprising a loop (or leaflet) shape andextending in an upward direction and a second pair of struts 132 a, 132b, each comprising a loop (or leaflet) shape and extending in a downwarddirection, generally in an opposite direction relative to at least thefirst pair of struts 130 a, 130 b. It should be noted that the termsupward and downward are used to describe the orientation of the firstand second segments 122, 124 relative to one another. More specifically,the first pair of struts 130 a, 130 b generally extend in an outwardinclination in a first direction relative to a longitudinal axis of themulti-segment end effector 114 and are spaced apart from one another.Similarly, the second pair of struts 132 a, 132 b extend in an outwardinclination in a second direction substantially opposite the firstdirection relative to the longitudinal axis of the multi-segment endeffector and spaced apart from one another.

The second set of support elements of the second segment 124, when inthe expanded deployed configuration, includes a second set of struts134(1), 134(2), 134(n) (approximately six struts), each comprising aloop shape extending outward to form an open-ended circumferentialshape. As shown, the open-ended circumferential shape generallyresembles a blooming flower, wherein each looped strut 134 may generallyresemble a flower petal. It should be noted that the second set ofstruts 134 may include any number of individual struts and is notlimited to six, as illustrated. For example, in some embodiments, thesecond segment 124 may include two, three, four, five, six, seven,eight, nine, ten, or more struts 134.

The first and second segments 122, 124, specifically struts 130, 132,and 134 include one or more energy delivery elements, such as aplurality of electrodes 136. It should be noted that any individualstrut may include any number of electrodes 136 and is not limited to oneelectrode, as shown. In the expanded state, the struts 130, 132, and 134can position any number of electrodes 136 against tissue at a targetsite within the nasal region (e.g., proximate to the palatine boneinferior to the SPF). The electrodes 136 can apply bipolar ormulti-polar radiofrequency (RF) energy to the target site totherapeutically modulate postganglionic parasympathetic nerves thatinnervate the nasal mucosa proximate to the target site. In variousembodiments, the electrodes 136 can be configured to apply pulsed RFenergy with a desired duty cycle (e.g., 1 second on/0.5 seconds off) toregulate the temperature increase in the target tissue.

The first and second segments 122, 124 and the associated struts 130,132, and 134 can have sufficient rigidity to support the electrodes 136and position or press the electrodes 136 against tissue at the targetsite. In addition, each of the expanded first and second segments 122,124 can press against surrounding anatomical structures proximate to thetarget site (e.g., the turbinates, the palatine bone, etc.) and theindividual struts 130, 132, 134 can at least partially conform to theshape of the adjacent anatomical structures to anchor the end effector114 In addition, the expansion and conformability of the struts 130,132, 134 can facilitate placing the electrodes 136 in contact with thesurrounding tissue at the target site. The electrodes 136 can be madefrom platinum, iridium, gold, silver, stainless steel, platinum-iridium,cobalt chromium, iridium oxide, polyethylenedioxythiophene (PEDOT),titanium, titanium nitride, carbon, carbon nanotubes, platinum grey,Drawn Filled Tubing (DFT) with a silver core, and/or other suitablematerials for delivery RF energy to target tissue. In some embodiments,such as illustrated in FIG. 6, a strut may include an outer jacketsurrounding a conductive wire, wherein portions of the outer jacket areselectively absent along a length of the strut, thereby exposing theunderlying conductive wire so as to act as an energy delivering element(i.e., an electrode) and/or sensing element, as described in greaterdetail herein.

In certain embodiments, each electrode 136 can be operated independentlyof the other electrodes 136. For example, each electrode can beindividually activated and the polarity and amplitude of each electrodecan be selected by an operator or a control algorithm (e.g., executed bythe controller 107 previously described herein. The selectiveindependent control of the electrodes 136 allows the end effector 114 todeliver RF energy to highly customized regions. For example, a selectportion of the electrodes 136 can be activated to target neural fibersin a specific region while the other electrodes 136 remain inactive. Incertain embodiments, for example, electrodes 136 may be activated acrossthe portion of the second segment 124 that is adjacent to tissue at thetarget site, and the electrodes 136 that are not proximate to the targettissue can remain inactive to avoid applying energy to non-targettissue. Such configurations facilitate selective therapeutic modulationof nerves on the lateral nasal wall within one nostril without applyingenergy to structures in other portions of the nasal cavity.

The electrodes 136 are electrically coupled to an RF generator (e.g.,the generator 106 of FIG. 1) via wires (not shown) that extend from theelectrodes 136, through the shaft 116, and to the RF generator. Wheneach of the electrodes 136 is independently controlled, each electrode136 couples to a corresponding wire that extends through the shaft 116.In other embodiments, multiple electrodes 116 can be controlled togetherand, therefore, multiple electrodes 116 can be electrically coupled tothe same wire extending through the shaft 116. As previously described,the RF generator and/or components operably coupled (e.g., a controlmodule) thereto can include custom algorithms to control the activationof the electrodes 136. For example, the RF generator can deliver RFpower at about 460-480 kHz (+ or −5 kHz) to the electrodes 136, and doso while activating the electrodes 136 in a predetermined patternselected based on the position of the end effector 114 relative to thetreatment site and/or the identified locations of the target nerves. TheRF generator is able to provide bipolar low power (10 watts with maximumsetting of 50 watts) RF energy delivery, and further providemultiplexing capabilities (across a maximum of 30 channels).

Once deployed, the first and second segments 122, 124 contact andconform to a shape of the respective locations, including conforming toand complementing shapes of one or more anatomical structures at therespective locations. In turn, the first and second segments 122, 124become accurately positioned within the nasal cavity to subsequentlydeliver, via one or more electrodes 136, precise and focused applicationof RF thermal energy to the one or more target sites to therebytherapeutically modulate associated neural structures. Morespecifically, the first and second segments 122, 124 have shapes andsizes when in the expanded configuration that are specifically designedto place portions of the first and second segments 122, 124, and thusone or more electrodes associated therewith 136, into contact withtarget sites within nasal cavity associated with postganglionicparasympathetic fibers that innervate the nasal mucosa.

For example, the first set of flexible support elements of the firstsegment 122 conforms to and complements a shape of a first anatomicalstructure at the first location when the first segment 122 is in thedeployed configuration and the second set of flexible support elementsof the second segment 124 conforms to and complements a shape of asecond anatomical structure at the second location when the secondsegment is in the deployed configuration. The first and secondanatomical structures may include, but are not limited to, inferiorturbinate, middle turbinate, superior turbinate, inferior meatus, middlemeatus, superior meatus, pterygopalatine region, pterygopalatine fossa,sphenopalatine foramen, accessory sphenopalatine foramen(ae), andsphenopalatine micro-foramen(ae).

In some embodiments, the first segment 122 of the multi-segment endeffector 114 is configured in a deployed configuration to fit around atleast a portion of a middle turbinate at an anterior position relativeto the middle turbinate and the second segment 124 of the multi-segmentend effector is configured in a deployed configuration to contact aplurality of tissue locations in a cavity at a posterior positionrelative to the middle turbinate.

For example, the first set of flexible support elements of the firstsegment (i.e., struts 130 and 132) conforms to and complements a shapeof a lateral attachment and posterior-inferior edge of the middleturbinate when the first segment 122 is in the deployed configurationand the second set of flexible support elements (i.e., struts 134) ofthe second segment 124 contact a plurality of tissue locations in acavity at a posterior position relative to the lateral attachment andposterior-inferior edge of middle turbinate when the second segment 124is in the deployed configuration. Accordingly, when in the deployedconfiguration, the first and second segments 122, 124 are configured toposition one or more associated electrodes 136 at one or more targetsites relative to either of the middle turbinate and the plurality oftissue locations in the cavity behind the middle turbinate. In turn,electrodes 136 are configured to deliver RF energy at a level sufficientto therapeutically modulate postganglionic parasympathetic nervesinnervating nasal mucosa at an innervation pathway within the nasalcavity of the patient.

As illustrated in FIG. 5E, the first segment 122 comprises a bilateralgeometry. In particular, the first segment 122 includes two identicalsides, including a first side formed of struts 130 a, 132 a and a secondside formed of struts 130 b, 132 b. This bilateral geometry allows atleast one of the two sides to conform to and accommodate an anatomicalstructure within the nasal cavity when the first segment 122 is in anexpanded state. For example, when in the expanded state, the pluralityof struts 130 a, 132 a contact multiple locations along multipleportions of the anatomical structure and electrodes provided by thestruts are configured to emit energy at a level sufficient to createmultiple micro-lesions in tissue of the anatomical structure thatinterrupt neural signals to mucus producing and/or mucosal engorgementelements. In particular, struts 130 a, 132 a conform to and complement ashape of a lateral attachment and posterior-inferior edge of the middleturbinate when the first segment 122 is in the deployed configuration,thereby allowing for both sides of the anatomical structure to receiveenergy from the electrodes. By having this independence between firstand second side (i.e., right and left side) configurations, the firstsegment 122 is a true bilateral device. By providing a bilateralgeometry, the multi-segment end effector 114 does not require a repeatuse configuration to treat the other side of the anatomical structure,as both sides of the structure are accounted at the same time due to thebilateral geometry. The resultant micro-lesion pattern can be repeatableand is predictable in both macro element (depth, volume, shapeparameter, surface area) and can be controlled to establish low to higheffects of each, as well as micro elements (the thresholding of effectswithin the range of the macro envelope can be controlled), as well bedescribed in greater detail herein. The systems of the present inventionare further able to establish gradients within allowing for control overneural effects without having widespread effect to other cellularbodies, as will be described in greater detail herein.

FIG. 7 is a cross-sectional view of a portion of the shaft 116 of thehandheld device taken along lines 7-7 of FIG. 4. As illustrated, theshaft 116 may be constructed from multiple components so as to have theability to constrain the end effector 114 in the retracted configuration(i.e., the low-profile delivery state) when the end effector 114 isretracted within the shaft 116, and to further provide an atraumatic,low profile and durable means to deliver the end effector 114 to thetarget site. The shaft 116 includes coaxial tubes which travel from thehandle 118 to a distal end of the shaft 116. The shaft 116 assembly islow profile to ensure trans-nasal delivery of therapy. The shaft 116includes an outer sheath 138, surrounding a hypotube 140, which isfurther assembled over electrode wires 129 which surround an inner lumen142. The outer sheath 138 serves as the interface between the anatomyand the device 102. The outer sheath 138 may generally include a lowfriction PTFE liner to minimize friction between the outer sheath 138and the hypotube 140 during deployment and retraction. In particular theouter sheath 138 may generally include an encapsulated braid along alength of the shaft 116 to provide flexibility while retaining kinkresistance and further retaining column and/or tensile strength. Forexample, the outer sheath 138 may include a soft Pebax material, whichis atraumatic and enables smooth delivery through the nasal passage. Theouter sheath 138 may further include orientation/landmark markings on anexterior surface thereof, generally at the distal end, wherein themarkings may provide a visual indication to an operator of thearchitecture and/or spatial orientation of first and/or second segments122, 124 of the end effector 114 to assist in positioning and deploymentof the end effector 114.

The hypotube 140 is assembled over the electrode wires starting withinthe handle 118 and travelling to the proximal end of the end effector114. The hypotube 140 generally acts to protect the wires duringdelivery and is malleable to enable flexibility without kinking tothereby improve trackability. The hypotube 140 provides stiffness andenables torqueability of the device 102 to ensure accurate placement ofthe end effector 114. The hypotube 140 also provides a low frictionexterior surface which enables low forces when the outer sheath 138moves relative to the hypotube 140 during deployment and retraction orconstraint. The shaft 116 may be pre-shaped in such a manner so as tocomplement the nasal cavity. For example, the hypotube 140 may beannealed to create a bent shaft 116 with a pre-set curve. The hypotube140 may include a stainless-steel tubing, for example, which interfaceswith a liner in the outer sheath 138 for low friction movement.

The inner lumen 142 may generally provide a channel for fluid extractionduring a treatment procedure. For example, the inner lumen 142 extendsfrom the distal end of the shaft 116 through the hypotube 140 and toatmosphere via a fluid line (line 121 of FIG. 4). The inner lumen 142materials are chosen to resist forces of external components actingthereon during a procedure.

FIG. 8 is a side view of the handle 118. FIG. 9 is a side view of thehandle 118 illustrating internal components enclosed within. The handle118 generally includes an ergonomically-designed grip portion whichprovides ambidextrous use for both left and right handed use andconforms to hand anthropometrics to allow for at least one of anoverhand grip style and an underhand grip style during use in aprocedure. For example, the handle 118 may include specific contours,including recesses 144, 146, and 148 which are designed to naturallyreceive one or more of an operator's fingers in either of an overhandgrip or underhand grip style and provide a comfortable feel for theoperator. For example, in an underhand grip, recess 144 may naturallyreceive an operator's index finger, recess 146 may naturally receive anoperator's middle finger, and recess 148 may naturally receive anoperator's ring and little (pinkie or pinky) fingers which wrap aroundthe proximal protrusion 150 and the operator's thumb naturally rests ona top portion of the handle 118 in a location adjacent to the firstmechanism 126. In an overhand grip, the operator's index finger maynaturally rest on the top portion of the handle 118, adjacent to thefirst mechanism 126, while recess 144 may naturally receive theoperator's middle finger, recess 146 may naturally receive a portion ofthe operator's middle and/or ring fingers, and recess 148 may naturallyreceive and rest within the space (sometimes referred to as thepurlicue) between the operator's thumb and index finger.

As previously described, the handle includes multiple user-operatedmechanisms, including at least a first mechanism 126 for deployment ofthe end effector 114 from the retracted configuration to the expandeddeployed configuration and a second mechanism 128 for controlling ofenergy output by the end effector, notably energy delivery from one ormore electrodes 136. As shown, the user inputs for the first and secondmechanisms 126, 128 are positioned a sufficient distance to one anotherto allow for simultaneous one-handed operation of both user inputsduring a procedure. For example, user input for the first mechanism 126is positioned on a top portion of the handle 118 adjacent the gripportion and user input for the second mechanism 128 is positioned onside portions of the handle 118 adjacent the grip portion. As such, inan underhand grip style, the operator's thumb rests on the top portionof the handle adjacent to the first mechanism 126 and at least theirmiddle finger is positioned adjacent to the second mechanism 128, eachof the first and second mechanisms 126, 128 accessible and able to beactuated. In an overhand grip system, the operator's index finger restson the top portion of the handle adjacent to the first mechanism 126 andat least their thumb is positioned adjacent to the second mechanism 128,each of the first and second mechanisms 126, 128 accessible and able tobe actuated. Accordingly, the handle accommodates various styles of gripand provides a degree of comfort for the surgeon, thereby furtherimproving execution of the procedure and overall outcome.

Referring to FIG. 9, the various components provided within the handle118 are illustrated. As shown, the first mechanism 126 may generallyinclude a rack and pinion assembly providing movement of the endeffector 114 between the retracted and deployed configurations inresponse to input from a user-operated controller. The rack and pinionassembly generally includes a set of gears 152 for receiving input fromthe user-operated controller and converting the input to linear motionof a rack member 154 operably associated with at least one of the shaft116 and the end effector 114. The rack and pinion assembly comprises agearing ratio sufficient to balance a stroke length and retraction anddeployment forces, thereby improving control over the deployment of theend effector. As shown, the rack member 154 may be coupled to a portionof the shaft 116, for example, such that movement of the rack member 154in a direction towards a proximal end of the handle 118 results incorresponding movement of the shaft 116 while the end effector 114remains stationary, thereby exposing the end effector 114 and allowingthe end effector 114 to transition from the constrained, retractedconfiguration to the expanded, deployed configuration. Similarly, uponmovement of the rack member 154 in a direction towards a distal end ofthe handle 118 results in corresponding movement of the shaft 116 whilethe end effector 114 remains stationary, thereby enclosing the endeffector 114 within the shaft 116. It should be noted that, in otherembodiments, the rack member 154 may be directly coupled to a portion ofthe end effector 114 such that movement of the rack member 154 resultsin corresponding movement of the end effector 114 while the shaft 116remains stationary, thereby transitioning the end effector 114 betweenthe retracted and deployed configurations.

The user-operated controller associated with the first mechanism 126 mayinclude a slider mechanism operably associated with the rack and pinionrail assembly. Movement of the slider mechanism in a rearward directiontowards a proximal end of the handle results in transitioning of the endeffector 114 to the deployed configuration and movement of the slidermechanism in a forward direction towards a distal end of the handleresults in transitioning of the end effector to the retractedconfiguration. In other embodiment, the user-operated controllerassociated with the first mechanism 126 may include a scroll wheelmechanism operably associated with the rack and pinion rail assembly.Rotation of the wheel in a rearward direction towards a proximal end ofthe handle results in transitioning of the end effector to the deployedconfiguration and rotation of the wheel in a forward direction towards adistal end of the handle results in transitioning of the end effector tothe retracted configuration.

The user-operated controller associated with the first mechanism 126 maygenerally provide a high degree of precision and control over thedeployment (and retraction) of the first and second segments 122, 124.For example, in some instances, the operator may wish to only deploy thesecond segment 124 during the procedure, while the first segment 122remains in the retracted configuration. The user-operated controllerallows for an operator to provide a sufficient degree of input (i.e.,slide the slider mechanism or scroll the scroll wheel to a specificposition) which results in only the second segment 124 transitioningfrom the retracted configuration to the deployed configuration (whilethe first segment 122 remains enclosed within the shaft 116 and in theretracted configuration). For example, in some embodiments, the endeffector 114 may further include a detent feature, such as a catch orsimilar element, positioned between the first and second segments 122,124 and configured to provide a surgeon with feedback, such as haptic ortactile feedback, during deployment of the end effector segments,alerting the surgeon when at least the second segment 124 is fullydeployed. In particular, as the surgeon slides the slider mechanism orscrolls the scroll wheel during deployment of the second segment 124,the detect feature (provided between the first and second segments 122,124) may then reach a portion of the shaft 116 and cause an increase inresistance on the slider mechanism or scroll wheel, thereby indicatingto the surgeon that the second segment 124 has been deployed and thefirst segment 122 remains in the retracted configuration. Accordingly,the surgeon can position and orient the second segment 124 as theydesire without concern over the first segment 122 as it remains in theretracted configuration. In turn, one the second segment 124 ispositioned at the desired target site, the surgeon may then deploy thefirst segment 122 to perform the procedure. Yet still, in someinstances, only the second segment 124 may be used to perform aprocedure (i.e., deliver energy to one or more target sites in contactwith the second segment 124) and, as such, the first segment 122 maynever be deployed.

The second mechanism 128 may generally include a user-operatedcontroller configured to be actuated between at least an active positionand an inactive position to thereby control delivery of energy from theend effector 114, notable delivery of energy from the electrodes 136.The user-operated controller may be multi-modal in that theuser-operated controller may be actuated between multiple positionsproviding different functions/modes. For example, upon a single userinput (i.e., single press of button associated within controller), thesecond mechanism may provide a baseline apposition/sensing checkfunction prior to modulation. Upon pressing and holding the controllerbutton for a pre-defined period of time, the energy output from the endeffector may be activated. Further, upon double-tapping the controllerbutton, energy output is deactivated.

Furthermore, the handle and/or the shaft may include markings thatprovide a surgeon with a spatial orientation of the end effector whilethe end effector is in a nasal cavity. FIG. 10 is a side view of thehandle 118 illustrating multiple markings on a distal end of the handle118 and FIG. 11 is a perspective view of a portion of the shaft 116illustrating multiple markings on a distal end thereof. In particular,multiple markings may be provided on the handle and/or shaft and providea visual indication of the spatial orientation of one or more portionsof the first segment and second segment of the end effector when in thedeployed configurations. The markings may include, for example, text,symbols, color-coding insignia, or the like. Thus, during initialplacement of the end effector, when in a retracted configuration andenclosed within the shaft, a surgeon can rely on the markings on thehandle and/or shaft as a visual indication of the spatial orientation ofthe end effector (e.g., linear, axial, and/or depth position) prior todeployment to thereby ensure that, once deployed, the end effector,including both the first and second segments, are positioned in theintended locations within the nasal cavity.

For example, the handle and/or shaft may include markings associatedwith each of the first pair of struts 130 a, 130 b and each of thesecond pair of struts 132 a, 132 b, so as to provide an operator with avisual indication as to the resulting spatial orientation andarchitecture of at least the first segment 122 when initially navigatingthe nasal cavity and delivering the distal end of the shaft 116 to atarget site, prior to deployment of the end effector 114. In otherwords, the markings provide an operator with an indication of theorientation of at least the first segment 122 of the end effector 114prior to deploying the end effector 114, thereby ensuring accuratepositioning at the desired location.

FIG. 12 is a partial cut-away side view illustrating one approach fordelivering an end effector 114 a target site within a nasal region inaccordance with embodiments of the present disclosure. As shown, thedistal portion of the shaft 116 extends into the nasal passage NP,through the inferior meatus IM between the inferior turbinate IT and thenasal sill NS, and around the posterior portion of the inferiorturbinate IT where the end effector 114 is deployed at a treatment site.The treatment site can be located proximate to the access point orpoints of postganglionic parasympathetic nerves (e.g., branches of theposterior nasal nerve and/or other parasympathetic neural fibers thatinnervate the nasal mucosa) into the nasal cavity. In other embodiments,the target site can be elsewhere within the nasal cavity depending onthe location of the target nerves.

In various embodiments, the distal portion of the shaft 116 may beguided into position at the target site via a guidewire (not shown)using an over-the-wire (OTW) or a rapid exchange (RX) technique. Forexample, the end effector 114 can include a channel for engaging theguidewire. Intraluminal delivery of the end effector 114 can includeinserting the guide wire into an orifice in communication with the nasalcavity (e.g., the nasal passage or mouth), and moving the shaft 116and/or the end effector 114 along the guide wire until the end effector114 reaches a target site (e.g., inferior to the SPF).

Yet still, in further embodiments, the neuromodulation device 102 can beconfigured for delivery via a guide catheter or introducer sheath (notshown) with or without using a guide wire. The introducer sheath canfirst be inserted intraluminally to the target site in the nasal region,and the distal portion of the shaft 116 can then be inserted through theintroducer sheath. At the target site, the end effector 114 can bedeployed through a distal end opening of the introducer sheath or a sideport of the introducer sheath. In certain embodiments, the introducersheath can include a straight portion and a pre-shaped portion with afixed curve (e.g., a 5 mm curve, a 4 mm curve, a 3 mm curve, etc.) thatcan be deployed intraluminally to access the target site. In thisembodiment, the introducer sheath may have a side port proximal to oralong the pre-shaped curved portion through which the end effector 114can be deployed. In other embodiments, the introducer sheath may be madefrom a rigid material, such as a metal material coated with aninsulative or dielectric material. In this embodiment, the introducersheath may be substantially straight and used to deliver the endeffector 114 to the target site via a substantially straight pathway,such as through the middle meatus MM (FIG. 3A).

Image guidance may be used to aid the surgeon's positioning andmanipulation of the distal portion of the shaft 116, as well as thedeployment and manipulation of the end effector 114, specifically thefirst and second segments 122 thereof. For example, an endoscope 100and/or other visualization device can be positioned to visualize thetarget site, the positioning of the end effector 114 at the target site,and/or the end effector 114 during therapeutic neuromodulation. Theendoscope 100 may be delivered proximate to the target site by extendingthrough the nasal passage NP and through the middle meatus MM betweenthe inferior and middle turbinates IT and MT. From the visualizationlocation within the middle meatus MM, the endoscope 100 can be used tovisualize the treatment site, surrounding regions of the nasal anatomy,and the end effector 114.

In some embodiments, the distal portion of the shaft 116 may bedelivered via a working channel extending through an endoscope, andtherefore the endoscope can provide direct in-line visualization of thetarget site and the end effector 114. In other embodiments, an endoscopeis incorporated with the end effector 114 and/or the distal portion ofthe shaft 116 to provide in-line visualization of the end effector 114and/or the surrounding nasal anatomy. In other embodiments, imageguidance can be provided with various other guidance modalities, such asimage filtering in the infrared (IR) spectrum to visualize thevasculature and/or other anatomical structures, computed tomography(CT), fluoroscopy, ultrasound, optical coherence tomography (OCT),and/or combinations thereof. Yet still, in some embodiments, imageguidance components may be integrated with the neuromodulation device102 to provide image guidance during positioning of the end effector114.

Once positioned at the target site, the therapeutic modulation may beapplied via the one or more electrodes 136 and/or other features of theend effector 114 to precise, localized regions of tissue to induce oneor more desired therapeutic neuromodulating effects to disruptparasympathetic motor sensory function. The end effector 114 canselectively target postganglionic parasympathetic fibers that innervatethe nasal mucosa at a target or treatment site proximate to or at theirentrance into the nasal region. For example, the end effector 114 can bepositioned to apply therapeutic neuromodulation at least proximate tothe SPF (FIG. 3A) to therapeutically modulate nerves entering the nasalregion via the SPF. The end effector 114 can also be positioned toinferior to the SPF to apply therapeutic neuromodulation energy acrossaccessory foramen and microforamina (e.g., in the palatine bone) throughwhich smaller medial and lateral branches of the posterior superiorlateral nasal nerve enter the nasal region. The purposeful applicationof the energy at the target site may achieve therapeutic neuromodulationalong all or at least a portion of posterior nasal neural fibersentering the nasal region. The therapeutic neuromodulating effects aregenerally a function of, at least in part, power, time, and contactbetween the energy delivery elements and the adjacent tissue. Forexample, in certain embodiments therapeutic neuromodulation of autonomicneural fibers are produced by applying RF energy at a power of about2-20 W (e.g., 5 W, 7 W, 10 W, etc.) for a time period of about 1-20sections (e.g., 5-10 seconds, 8-10 seconds, 10-12 seconds, etc.).

The therapeutic neuromodulating effects may include partial or completedenervation via thermal ablation and/or non-ablative thermal alterationor damage (e.g., via sustained heating and/or resistive heating).Desired thermal heating effects may include raising the temperature oftarget neural fibers above a desired threshold to achieve non-ablativethermal alteration, or above a higher temperature to achieve ablativethermal alteration. For example, the target temperature may be abovebody temperature (e.g., approximately 37° C.) but less than about 90° C.(e.g., 70-75° C.) for non-ablative thermal alteration, or the targettemperature may be about 100° C. or higher (e.g., 110° C., 120° C.,etc.) for the ablative thermal alteration. Desired non-thermalneuromodulation effects may include altering the electrical signalstransmitted in a nerve.

Sufficiently modulating at least a portion of the parasympathetic nervesis expected to slow or potentially block conduction of autonomic neuralsignals to the nasal mucosa to produce a prolonged or permanentreduction in nasal parasympathetic activity. This is expected to reduceor eliminate activation or hyperactivation of the submucosal glands andvenous engorgement and, thereby, reduce or eliminate the symptoms ofrhinosinusitis. Further, because the device 102 applies therapeuticneuromodulation to the multitude of branches of the posterior nasalnerves rather than a single large branch of the posterior nasal nervebranch entering the nasal cavity at the SPF, the device 102 provides amore complete disruption of the parasympathetic neural pathway thataffects the nasal mucosa and results in rhinosinusitis. Accordingly, thedevice 102 is expected to have enhanced therapeutic effects for thetreatment of rhinosinusitis and reduced re-innervation of the treatedmucosa.

In other embodiments, the device 102 can be configured totherapeutically modulate nerves and/or other structures to treatdifferent indications. For example, the device 102 can be used totherapeutically modulate nerves that innervate the para-nasal sinuses totreat chronic sinusitis. In further embodiments, the system 100 and thedevice 102 disclosed herein can be configured therapeutically modulatethe vasculature within the nasal anatomy to treat other indications,such as epistaxis (i.e., excessive bleeding from the nose). For example,the system 100 and the device 102 devices described herein can be usedto apply therapeutically effective energy to arteries (e.g., thesphenopalatine artery and its branches) as they enter the nasal cavity(e.g., via the SPF, accessory foramen, etc.) to partially or completelycoagulate or ligate the arteries. In other embodiments, the system 100and the device 102 can be configured to partially or completelycoagulate or ligate veins and/or other vessels. For such embodiments inwhich the end effector 114 ligates or coagulates the vasculature, thesystem 100 and device 102 would be modified to deliver energy atsignificantly higher power (e.g., about 100 W) and/or longer times(e.g., 1 minute or longer) than would be required for therapeuticneuromodulation.

FIG. 13 is a flow diagram illustrating one embodiment of a method 400for treating a condition within a nasal cavity of a patient. The method400 includes advancing a multi-segment end effector within the nasalcavity of the patient (operation 410) wherein the multi-segment endeffector includes a first segment spaced apart from a second segment.The multi-segment end effector is retractable and expandable such that,once delivered to the one more target sites within the nasal cavity, thefirst and second segments can expand to a specific shape and/or sizecorresponding to anatomical structures within the nasal cavity andassociated with the target sites. The method 400 further includesdeploying the first and second segments at respective first and secondlocations within the nasal cavity (operation 420). In particular, eachof the first and second flexible segments includes a specific geometrywhen in a deployed configuration to complement anatomy of respectivelocations within the nasal cavity. Accordingly, once deployed, the firstand second segments contact and conform to a shape of the respectivelocations, including conforming to and complementing shapes of one ormore anatomical structures at the respective locations. The method 400further includes delivering energy, via the first and second segments,to tissue at one or more target sites with respect to the first andsecond locations (operation 430). In particular, the first and secondsegments become accurately positioned within the nasal cavity tosubsequently deliver, via one or more electrodes, precise and focusedapplication of RF thermal energy to the one or more target sites tothereby therapeutically modulate associated neural structures. The firstand second segments have shapes and sizes when in the expandedconfiguration that are specifically designed to place portions of thefirst and second segments, and thus one or more electrodes associatedtherewith, into contact with target sites within nasal cavity associatedwith postganglionic parasympathetic fibers that innervate the nasalmucosa.

FIG. 14 is a flow diagram illustrating another embodiment of a method500 for treating a condition within a nasal cavity of a patient. Themethod 500 includes providing a treatment device comprising an endeffector transformable between a retracted configuration and an expandeddeployed configuration, a shaft operably associated with the endeffector, and a handle operably associated with the shaft (operation510). The method 500 further includes advancing the end effector to oneor more target sites within the nasal cavity of the patient (operation520). The shaft may include a pre-defined shape (i.e., bent or angled ata specific orientation) so as to assist the operation for placement ofthe end effector at the target sites. The handle includes anergonomically-designed grip portion which provides ambidextrous use forboth left and right handed use and conforms to hand anthropometrics toallow for at least one of an overhand grip style and an underhand gripstyle during use in a procedure.

The handle and/or the shaft may include markings (e.g., text, symbols,color-coding insignia, etc.) that provide a surgeon with a spatialorientation of the end effector while the end effector is in a nasalcavity. In particular, multiple markings may be provided on the handleand/or shaft and provide a visual indication of the spatial orientationof one or more portions of the first segment and second segment of theend effector when in the deployed configurations. Thus, during initialplacement of the end effector, when in a retracted configuration andenclosed within the shaft, a surgeon can rely on the markings on thehandle and/or shaft as a visual indication of the spatial orientation ofthe end effector (e.g., linear, axial, and/or depth position) prior todeployment to thereby ensure that, once deployed, the end effector,including both the first and second segments, are positioned in theintended locations within the nasal cavity.

The method 500 further includes deploying the end effector at the one ormore target sites (operation 530) and delivering energy from the endeffector to tissue at the one or more target sites (operation 540). Thehandle includes multiple user-operated mechanisms, including at least afirst mechanism for deployment of the end effector from the retractedconfiguration to the expanded deployed configuration and a secondmechanism for controlling of energy output by the end effector. The userinputs for the first and second mechanisms are positioned a sufficientdistance to one another to allow for simultaneous one-handed operationof both user inputs during a procedure. Accordingly, the handleaccommodates various styles of grip and provides a degree of comfort forthe surgeon, thereby further improving execution of the procedure andoverall outcome.

FIG. 15 is a flow diagram illustrating another embodiment of a method600 for treating a condition within a nasal cavity of a patient. Themethod 600 includes providing a treatment device comprising amulti-segment end effector, including a proximal segment that is spacedapart from a distal segment, and a visual marker (operation 610). Aspreviously described herein, the visual marker may be provided by ashaft, for example, operably associated with the multi-segment endeffector. The visual marker may be in the form of text, symbols,color-coding insignia, or the like, that generally provides a user(i.e., a surgeon or other medical professional) with a visual indicationof a spatial orientation of one or more portions of the proximal segmentwhile the multi-segment end effector is in a nasal cavity.

The method 600 further includes advancing, under image guidance, theproximal segment and the distal segment through a nasal cavity of apatient and past a middle turbinate (operation 620) and deploying thedistal segment from a retracted configuration to an expandedconfiguration (operation 630). The image guidance may be in the form ofan endoscope and/or other visualization device that can be positioned toso as to provide visualization to the user of one or more locationswithin the nasal cavity and to further provide visualization of themulti-segment end effector and other portions of the treatment device(i.e., at least a distal portion of the shaft with a visual marker)during advancement into the nasal cavity to assist the user in placementof the multi-segment end effector.

Upon deploying the distal segment to an expanded configuration, themethod 600 further includes aligning, under the image guidance and withreference to the visual marker, the proximal segment with respect to themiddle turbinate (operation 640). The visual marker may be provided onthe shaft, for example, and provide a visual indication of the spatialorientation of one or more portions of the proximal segment when in thedeployed configuration. For example, the deployed proximal segment mayinclude a geometry to complement a shape of the middle turbinate. Morespecifically, the proximal segment may include a set of flexible supportelements that conform to and complement a shape of the middle turbinatewhen the proximal segment is in the deployed expanded configuration. Thevisual marker, provided by the shaft, provides a visual indication ofthe spatial orientation of one or more portions of the proximal segment,including, for example, a spatial orientation of the set of flexiblesupport elements when in a deployed expanded configuration. Accordingly,aligning the proximal segment with respect to the middle turbinateincludes the user positioning, under the image guidance, the shaft andassociated visual marker relative to the middle turbinate.

Thus, during initial placement of at least the proximal segment when itis in a retracted configuration, a surgeon can rely on the markings onthe shaft as a visual indication of the spatial orientation (e.g.,linear, axial, and/or depth position) of one or more portions of theproximal segment prior to its deployment, thereby ensuring that, oncedeployed, the proximal segment is positioned in the intended locationwithin the nasal cavity.

The method 600 further includes deploying the proximal segment aroundthe middle turbinate and advancing the deployed proximal segment towardthe middle turbinate to establish contact and secure the proximalsegment to the middle turbinate (operation 650). Again, the set offlexible support elements of the proximal segment are able to conform toand complement a shape of the middle turbinate when the proximal segmentis in the deployed expanded configuration, thereby ensuring that thedeployed proximal segment is secured to the middle turbinate.

It should be noted that the treatment device further includes a handleoperably associated with the multi-segment end effector and the shaft.The handle generally includes a controller mechanism for providingindependent, controlled deployment of each of the proximal and distalsegments from a retracted configuration to an expanded configurationwithin the nasal cavity. In particular, in some embodiments, thecontroller mechanism includes a rack and pinion assembly providingmovement of the at least one of the proximal and distal segments betweenthe retracted configuration and expanded configuration in response touser input from an associated user-operated controller. The rack andpinion assembly may include, for example, a set of gears for receivinguser input from the user-operated controller and converting the userinput to linear motion of a rack member operably associated with themulti-segment end effector.

The controller mechanism may further include a detent feature positionedrelative to the proximal and distal segments and configured to provideactive feedback to a user indicative of deployment of at least one ofthe proximal and distal segments. The active feedback may be in the formhaptic feedback provided by the controller mechanism. For example, thehaptic feedback may include an increase or decrease in resistanceassociated with user input with the controller mechanism forcorresponding movement of the at least one of the proximal and distalsegments between retracted and expanded configurations, and/orconfigurations therebetween (i.e., a plurality of configurations betweena fully retracted configuration and a fully expanded configuration). Forexample, upon deploying the distal segment, the controller mechanism, asa result of interaction with the detent, may provide haptic feedback, inthe form of a vibration or other motion (e.g., click(s) or change inresistance), to the user via the user-operated controller. The hapticfeedback may indicate to the user that the distal segment is fullydeployed and any further input with the user-operated controller willresult in deployment of the proximal segment. The controller mechanismmay further provide specific haptic feedback during deployment of agiven segment, such as deployment of the proximal segment. For example,the haptic feedback may be in the form of an increase or decrease inresistance upon the user-operated controller, for example, whichcorresponds to the degree to which the proximal segment is deployed.

In some embodiments, the controller mechanism may further include afriction-based feature configured to provide stable movement of at leastone of the proximal and distal segments between the retracted andexpanded configurations and further provide active feedback to a userindicative of deployment of at least one of the proximal and distalsegments. The friction-based feature may include, for example, a lockmechanism configured to provide constant friction between one or moreportions of the rack and pinion assembly sufficient to maintain aposition of at least one of the proximal and distal segments duringdeployment thereof.

For example, the constant friction may be sufficient to hold either ofthe proximal or distal segments in a certain position as the segmenttransitions between retracted and expanded configurations regardless ofwhether the user maintains contact with the user-operated controller. Inother words, a user does not need to maintain contact with theuser-operated controller in order to ensure that the proximal or distalsegment holds a certain position during deployment thereof. Rather, auser can simply interact with the user-operated controller to transitionone of the proximal and distal segments to a desired configuration andthe constant friction provided by the locking mechanism is sufficient tomaintain the configuration of proximal or distal segment in the eventthat the user goes hands free (i.e., removes any contact with theuser-operated controller). The constant friction is of a levelsufficient to prevent undesired movement of the proximal or distalsegments (i.e., unintended collapsing or expanding), while stillallowing for a user to overcome such friction to move the proximal ordistal segment to a desired configuration upon user input with theuser-operated controller.

In some embodiments, the user-operated controller includes a slidermechanism operably associated with the rack and pinion rail assembly,wherein movement of the slider mechanism in a first direction results intransitioning of at least one of the proximal and distal segments to anexpanded configuration and movement of the slider mechanism in a secondopposite direction results in transitioning of at least one of theproximal and distal segments to the retracted configuration. In otherembodiments, the user-operated controller includes a scroll wheelmechanism operably associated with the rack and pinion rail assembly,wherein rotation of the wheel in a first direction results intransitioning of at least one of the proximal and distal segments to anexpanded configuration and rotation of the wheel in a second oppositedirection results in transitioning of at least one of the proximal anddistal segments to the retracted configuration. As such, duringdeployment of the proximal segment, the slider mechanism or scroll wheelmay provide increased resistance to a user as the user transitions theproximal segment from a fully retracted configuration to a fullydeployed configuration.

Accordingly, during deployment of either of the distal and proximalsegments, the controller mechanism provides active feedback to the user,wherein such active feedback can be indicative of which segment is beingactively controlled and/or the extent of deployment of either of thedistal or proximal segments, thereby improving user control over thedeployment of either of the distal and proximal segments.

Upon securing the proximal segment to the middle turbinate, the method600 further includes delivering energy, via the proximal segment, to themiddle turbinate to treat a condition (operation 660). The condition mayinclude, but is not limited to, allergic rhinitis, non-allergicrhinitis, chronic rhinitis, acute rhinitis, chronic sinusitis, acutesinusitis, chronic rhinosinusitis, acute rhinosinusitis, and medicalresistant rhinitis, and a combination thereof. In some embodiments,delivering energy from the proximal segment includes deliveringradiofrequency (RF) energy, via one or more electrodes provided by theproximal segment, to tissue of the middle turbinate at one or moretarget sites, wherein the one or more target sites are associated withparasympathetic nerve supply. In some embodiments, RF energy isdelivered, via the one or more electrodes provided by the proximalsegment, at a level sufficient to therapeutically modulatepostganglionic parasympathetic nerves innervating nasal mucosa at aninnervation pathway within the nasal cavity of the patient.

Accordingly, the handheld device of the present invention provides auser-friendly, non-invasive means of treating rhinosinusitis conditions,including precise and focused application of RF thermal energy to theintended target sites for therapeutic modulation of the intended neuralstructures without causing collateral and unintended damage ordisruption to other neural structures. Thus, the efficacy of a vidianneurectomy procedure can be achieved with the systems and methods of thepresent invention without the drawbacks discussed above. Most notably,the handheld device provides a surgeon with a user-friendly,non-invasive, and precise means for treating rhinorrhea and othersymptoms of rhinosinusitis by targeting only those specific neuralstructures associated with such conditions, notably postganglionicparasympathetic nerves innervating nasal mucosa, thereby disrupting theparasympathetic nerve supply and interrupting parasympathetic tone.Accordingly, such treatment is effective at treating rhinosinusitisconditions while greatly reducing the risk of causing lateral damage ordisruption to other nerve fibers, thereby reducing the likelihood ofunintended complications and side effects.

Neuromodulation Monitoring, Feedback, and Mapping Capabilities

As previously described, the system 100 includes a console 104 to whichthe device 102 is to be connected. The console 104 is configured toprovide various functions for the neuromodulation device 102, which mayinclude, but is not limited to, controlling, monitoring, supplying,and/or otherwise supporting operation of the neuromodulation device 102.The console 104 can further be configured to generate a selected formand/or magnitude of energy for delivery to tissue or nerves at thetarget site via the end effector 114, and therefore the console 104 mayhave different configurations depending on the treatment modality of thedevice 102. For example, when device 102 is configured forelectrode-based, heat-element-based, and/or transducer-based treatment,the console 104 includes an energy generator 106 configured to generateRF energy (e.g., monopolar, bipolar, or multi-polar RF energy), pulsedelectrical energy, microwave energy, optical energy, ultrasound energy(e.g., intraluminally-delivered ultrasound and/or HIFU), direct heatenergy, radiation (e.g., infrared, visible, and/or gamma radiation),and/or another suitable type of energy. When the device 102 isconfigured for cryotherapeutic treatment, the console 104 can include arefrigerant reservoir (not shown), and can be configured to supply thedevice 102 with refrigerant. Similarly, when the device 102 isconfigured for chemical-based treatment (e.g., drug infusion), theconsole 104 can include a chemical reservoir (not shown) and can beconfigured to supply the device 102 with one or more chemicals.

In some embodiments, the console 104 may include a controller 107communicatively coupled to the neuromodulation device 102. However, inthe embodiments described herein, the controller 107 may generally becarried by and provided within the handle 118 of the neuromodulationdevice 102. The controller 107 is configured to initiate, terminate,and/or adjust operation of one or more electrodes provided by the endeffector 114 directly and/or via the console 104. For example, thecontroller 107 can be configured to execute an automated controlalgorithm and/or to receive control instructions from an operator (e.g.,surgeon or other medical professional or clinician). For example, thecontroller 107 and/or other components of the console 104 (e.g.,processors, memory, etc.) can include a computer-readable mediumcarrying instructions, which when executed by the controller 107, causesthe device 102 to perform certain functions (e.g., apply energy in aspecific manner, detect impedance, detect temperature, detect nervelocations or anatomical structures, perform nerve mapping, etc.). Amemory includes one or more of various hardware devices for volatile andnon-volatile storage, and can include both read-only and writablememory. For example, a memory can comprise random access memory (RAM),CPU registers, read-only memory (ROM), and writable non-volatile memory,such as flash memory, hard drives, floppy disks, CDs, DVDs, magneticstorage devices, tape drives, device buffers, and so forth. A memory isnot a propagating signal divorced from underlying hardware; a memory isthus non-transitory.

The console 104 may further be configured to provide feedback to anoperator before, during, and/or after a treatment procedure viamapping/evaluation/feedback algorithms 110. For example, themapping/evaluation/feedback algorithms 110 can be configured to provideinformation associated with the location of nerves at the treatmentsite, the location of other anatomical structures (e.g., vessels) at thetreatment site, the temperature at the treatment site during monitoringand modulation, and/or the effect of the therapeutic neuromodulation onthe nerves at the treatment site. In certain embodiments, themapping/evaluation/feedback algorithm 110 can include features toconfirm efficacy of the treatment and/or enhance the desired performanceof the system 100. For example, the mapping/evaluation/feedbackalgorithm 110, in conjunction with the controller 107 and the endeffector 114, can be configured to monitor neural activity and/ortemperature at the treatment site during therapy and automatically shutoff the energy delivery when the neural activity and/or temperaturereaches a predetermined threshold (e.g., a threshold reduction in neuralactivity, a threshold maximum temperature when applying RF energy, or athreshold minimum temperature when applying cryotherapy). In otherembodiments, the mapping/evaluation/feedback algorithm 110, inconjunction with the controller 107, can be configured to automaticallyterminate treatment after a predetermined maximum time, a predeterminedmaximum impedance or resistance rise of the targeted tissue (i.e., incomparison to a baseline impedance measurement), a predetermined maximumimpedance of the targeted tissue), and/or other threshold values forbiomarkers associated with autonomic function. This and otherinformation associated with the operation of the system 100 can becommunicated to the operator via a display 112 (e.g., a monitor,touchscreen, user interface, etc.) on the console 104 and/or a separatedisplay (not shown) communicatively coupled to the console 104.

In various embodiments, the end effector 114 and/or other portions ofthe system 100 can be configured to detect variousbioelectric-parameters of the tissue at the target site, and thisinformation can be used by the mapping/evaluation/feedback algorithms110 to determine the anatomy at the target site (e.g., tissue types,tissue locations, vasculature, bone structures, foramen, sinuses, etc.),locate neural structures, differentiate between different types ofneural structures, map the anatomical and/or neural structure at thetarget site, and/or identify neuromodulation patterns of the endeffector 114 with respect to the patient's anatomy. For example, the endeffector 114 can be used to detect resistance, complex electricalimpedance, dielectric properties, temperature, and/or other propertiesthat indicate the presence of neural fibers and/or other anatomicalstructures in the target region. In certain embodiments, the endeffector 114, together with the mapping/evaluation/feedback algorithms110, can be used to determine resistance (rather than impedance) of thetissue (i.e., the load) to more accurately identify the characteristicsof the tissue. The mapping/evaluation/feedback algorithms 110 candetermine resistance of the tissue by detecting the actual power andcurrent of the load (e.g., via the electrodes 136).

In some embodiments, the system 100 provides resistance measurementswith a high degree of accuracy and a very high degree of precision, suchas precision measurements to the hundredths of an Ohm (e.g., 0.01Ω) forthe range of 1-50Ω. The high degree of resistance detection accuracyprovided by the system 100 allows for the detection sub-microscalestructures, including the firing of neural structures, differencesbetween neural structures and other anatomical structures (e.g., bloodvessels), and event different types of neural structures. Thisinformation can be analyzed by the mapping/evaluation/feedbackalgorithms and/or the controller 107 and communicated to the operatorvia a high resolution spatial grid (e.g., on the display 112) and/orother type of display to identify neural structures and other anatomy atthe treatment site and/or indicate predicted neuromodulation regionsbased on the ablation pattern with respect to the mapped anatomy.

As previously described, in certain embodiments, each electrode 136 canbe operated independently of the other electrodes 136. For example, eachelectrode can be individually activated and the polarity and amplitudeof each electrode can be selected by an operator or a control algorithmexecuted by the controller 107. The selective independent control of theelectrodes 136 allows the end effector 114 to detect information anddeliver RF energy to highly customized regions. For example, a selectportion of the electrodes 136 can be activated to target specific neuralfibers in a specific region while the other electrodes 136 remaininactive. In certain embodiments, for example, electrodes 136 may beactivated across the portion of the second segment 124 that is adjacentto tissue at the target site, and the electrodes 136 that are notproximate to the target tissue can remain inactive to avoid applyingenergy to non-target tissue. In addition, the electrodes 136 can beindividually activated to stimulate or therapeutically modulate certainregions in a specific pattern at different times (e.g., viamultiplexing), which facilitates detection of anatomical parametersacross a zone of interest and/or regulated therapeutic neuromodulation.

The electrodes 136 can be electrically coupled to the energy generator106 via wires (not shown) that extend from the electrodes 136, throughthe shaft 116, and to the energy generator 106. When each of theelectrodes 136 is independently controlled, each electrode 136 couplesto a corresponding wire that extends through the shaft 116. This allowseach electrode 136 to be independently activated for stimulation orneuromodulation to provide precise ablation patterns and/or individuallydetected via the console 104 to provide information specific to eachelectrode 136 for neural or anatomical detection and mapping. In otherembodiments, multiple electrodes 136 can be controlled together and,therefore, multiple electrodes 136 can be electrically coupled to thesame wire extending through the shaft 116. The energy generator 16and/or components (e.g., a control module) operably coupled thereto caninclude custom algorithms to control the activation of the electrodes136. For example, the RF generator can deliver RF power at about 200-100W to the electrodes 136, and do so while activating the electrodes 136in a predetermined pattern selected based on the position of the endeffector 114 relative to the treatment site and/or the identifiedlocations of the target nerves. In other embodiments, the energygenerator 106 delivers power at lower levels (e.g., less than 1 W, 1-5W, 5-15 W, 15-50 W, 50-150 W, etc.) for stimulation and/or higher powerlevels. For example, the energy generator 106 can be configured todelivery stimulating energy pulses of 1-3 W via the electrodes 136 tostimulate specific targets in the tissue.

As previously described, the end effector 114 can further include one ormore temperature sensors disposed on the flexible first and secondsegments 122, 124 and/or other portions of the end effector 114 andelectrically coupled to the console 104 via wires (not shown) thatextend through the shaft 116. In various embodiments, the temperaturesensors can be positioned proximate to the electrodes 136 to detect thetemperature at the interface between tissue at the target site and theelectrodes 136. In other embodiments, the temperature sensors canpenetrate the tissue at the target site (e.g., a penetratingthermocouple) to detect the temperature at a depth within the tissue.The temperature measurements can provide the operator or the system withfeedback regarding the effect of the therapeutic neuromodulation on thetissue. For example, in certain embodiments the operator may wish toprevent or reduce damage to the tissue at the treatment site (e.g., thenasal mucosa), and therefore the temperature sensors can be used todetermine if the tissue temperature reaches a predetermined thresholdfor irreversible tissue damage. Once the threshold is reached, theapplication of therapeutic neuromodulation energy can be terminated toallow the tissue to remain intact and avoid significant tissue sloughingduring wound healing. In certain embodiments, the energy delivery canautomatically terminate based on the mapping/evaluation/feedbackalgorithm 110 stored on the console 104 operably coupled to thetemperature sensors.

In certain embodiments, the system 100 can determine the locationsand/or morphology of neural structures and/or other anatomicalstructures before therapy such that the therapeutic neuromodulation canbe applied to precise regions including target neural structures, whileavoiding negative effects on non-target structures, such as bloodvessels. As described in further detail below, the system 100 can detectvarious bioelectrical parameters in an interest zone (e.g., within inthe nasal cavity) to determine the location and morphology of variousneural structures (e.g., different types of neural structures, neuronaldirectionality, etc.) and/or other tissue (e.g., glandular structures,vessels, bony regions, etc.). In some embodiments, the system 100 isconfigured to measure bioelectric potential. To do so, one or more ofthe electrodes 136 is placed in contact with an epithelial surface at aregion of interest (e.g., a treatment site). Electrical stimuli (e.g.,constant or pulsed currents at one or more frequencies) are applied tothe tissue by one or more electrodes 136 at or near the treatment site,and the voltage and/or current differences at various differentfrequencies between various pairs of electrodes 136 of the end effector114 may be measured to produce a spectral profile or map of the detectedbioelectric potential, which can be used to identify different types oftissues (e.g., vessels, neural structures, and/or other types of tissue)in the region of interest. For example, current (i.e., direct oralternating current) can be applied to a pair of electrodes 136 adjacentto each other and the resultant voltages and/or currents between otherpairs of adjacent electrodes 136 are measured. It will be appreciatedthat the current injection electrodes 136 and measurement electrodes 136need not be adjacent, and that modifying the spacing between the twocurrent injection electrodes 136 can affect the depth of the recordedsignals. For example, closely-spaced current injection electrodes 136provided recorded signals associated with tissue deeper from the surfaceof the tissue than further spaced apart current injection electrodes 136that provide recorded signals associated with tissue at shallowerdepths. Recordings from electrode pairs with different spacings may bemerged to provide additional information on depth and localization ofanatomical structures.

Further, complex impedance and/or resistance measurements of the tissueat the region of interest can be detected directly from current-voltagedata provided by the bioelectric potential measurements while differinglevels of frequency currents are applied to the tissue (e.g., via theend effector 114), and this information can be used to map the neuraland anatomical structures by the use of frequency differentiationreconstruction. Applying the stimuli at different frequencies willtarget different stratified layers or cellular bodies or clusters. Athigh signal frequencies (e.g., electrical injection or stimulation), forexample, cell membranes of the neural structures do not impede currentflow, and the current passes directly through the cell membranes. Inthis case, the resultant measurement (e.g., impedance, resistance,capacitance, and/or induction) is a function of the intracellular andextracellular tissue and liquids. At low signal frequencies, themembranes impede current flow to provide different definingcharacteristics of the tissues, such as the shapes of the cells or cellspacing. The stimulation frequencies can be in the megahertz range, inthe kilohertz range (e.g., 400-500 kHz, 450-480 kHz, etc.), and/or otherfrequencies attuned to the tissue being stimulated and thecharacteristics of the device being used. The detected complex impedanceor resistances levels from the zone of interest can be displayed to theuser (e.g., via the display 112) to visualize certain structures basedon the stimulus frequency.

Further, the inherent morphology and composition of the anatomicalstructures in the nasal region react differently to differentfrequencies and, therefore, specific frequencies can be selected toidentify very specific structures. For example, the morphology orcomposition of targeted structures for anatomical mapping may depend onwhether the cells of tissue or other structure are membranonic,stratified, and/or annular. In various embodiments, the appliedstimulation signals can have predetermined frequencies attuned tospecific neural structures, such as the level of myelination and/ormorphology of the myelination. For example, second axonalparasympathetic structures are poorly myelinated than sympathetic nervesor other structures and, therefore, will have a distinguishable response(e.g., complex impedance, resistance, etc.) with respect to a selectedfrequency than sympathetic nerves. Accordingly, applying signals withdifferent frequencies to the target site can distinguish the targetedparasympathetic nerves from the non-targeted sensory nerves, andtherefore provide highly specific target sites for neural mapping beforeor after therapy and/or neural evaluation post-therapy. In someembodiments, the neural and/or anatomical mapping includes measuringdata at a region of interest with at least two different frequencies toidentify certain anatomical structures such that the measurements aretaken first based on a response to an injection signal having a firstfrequency and then again based on an injection signal having a secondfrequency different from the first. For example, there are twofrequencies at which hypertrophied (i.e., disease-state characteristics)sub-mucosal targets have a different electrical conductivity orpermittivity compared to “normal” (i.e., healthy) tissue. Complexconductivity may be determined based on one or more measuredphysiological parameters (e.g., complex impedance, resistance,dielectric measurements, dipole measurements, etc.) and/or observance ofone or more confidently known attributes or signatures. Furthermore, thesystem 100 can also apply neuromodulation energy via the electrodes 136at one or more predetermined frequencies attuned to a target neuralstructure to provide highly targeted ablation of the selected neuralstructure associated with the frequency(ies). This highly targetedneuromodulation also reduces the collateral effects of neuromodulationtherapy to non-target sites/structures (e.g., blood vessels) because thetargeted signal (having a frequency tuned to a target neural structure)will not have the same modulating effects on the non-target structures.

Accordingly, bioelectric properties, such as complex impedance andresistance, can be used by the system 100 before, during, and/or afterneuromodulation therapy to guide one or more treatment parameters. Forexample, before, during, and/or after treatment, impedance or resistancemeasurements may be used to confirm and/or detect contact between one ormore electrodes 136 and the adjacent tissue. The impedance or resistancemeasurements can also be used to detect whether the electrodes 136 areplaced appropriately with respect to the targeted tissue type bydetermining whether the recorded spectra have a shape consistent withthe expected tissue types and/or whether serially collected spectra werereproducible. In some embodiments, impedance or resistance measurementsmay be used to identify a boundary for the treatment zone (e.g.,specific neural structures that are to be disrupted), anatomicallandmarks, anatomical structures to avoid (e.g., vascular structures orneural structures that should not be disrupted), and other aspects ofdelivering energy to tissue.

The bioelectric information can be used to produce a spectral profile ormap of the different anatomical features tissues at the target site, andthe anatomical mapping can be visualized in a 3D or 2D image via thedisplay 112 and/or other user interface to guide the selection of asuitable treatment site. This neural and anatomical mapping allows thesystem 100 to accurately detect and therapeutically modulate thepostganglionic parasympathetic neural fibers that innervate the mucosaat the numerous neural entrance points into the nasal cavity. Further,because there are not any clear anatomical markers denoting the locationof the SPF, accessory foramen, and microforamina, the neural mappingallows the operator to identify and therapeutically modulate nerves thatwould otherwise be unidentifiable without intricate dissection of themucosa. In addition, anatomical mapping also allows the clinician toidentify certain structures that the clinician may wish to avoid duringtherapeutic neural modulation (e.g., certain arteries). The neural andanatomical bioelectric properties detected by the system 100 can also beused during and after treatment to determine the real-time effect of thetherapeutic neuromodulation on the treatment site. For example, themapping/evaluation/feedback algorithms 110 can also compare the detectedneural locations and/or activity before and after therapeuticneuromodulation, and compare the change in neural activity to apredetermined threshold to assess whether the application of therapeuticneuromodulation was effective across the treatment site.

In various embodiments, the system 100 can also be configured to map theexpected therapeutic modulation patterns of the electrodes 136 atspecific temperatures and, in certain embodiments, take into accounttissue properties based on the anatomical mapping of the target site.For example, the system 100 can be configured to map the ablationpattern of a specific electrode ablation pattern at the 45° C. isotherm,the 55° C. isotherm, the 65° C. isotherm, and/or othertemperature/ranges (e.g., temperatures ranging from 45° C. to 70° C. orhigher) depending on the target site and/or structure.

The system 100 may provide, via the display 112, three-dimensional viewsof such projected ablation patterns of the electrodes 136 of the endeffector 114. The ablation pattern mapping may define a region ofinfluence that each electrode 136 has on the surrounding tissue. Theregion of influence may correspond to the region of tissue that would beexposed to therapeutically modulating energy based on a definedelectrode activation pattern (i.e., one, two, three, four, or moreelectrodes on any given strut of the first and second segments 122,124). In other words, the ablation pattern mapping can be used toillustrate the ablation pattern of any number of electrodes 136, anygeometry of the electrode layout, and/or any ablation activationprotocol (e.g., pulsed activation, multi-polar/sequential activation,etc.).

In some embodiments, the ablation pattern may be configured such thateach electrode 136 has a region of influence surrounding only theindividual electrode 136 (i.e., a “dot” pattern). In other embodiments,the ablation pattern may be such that two or more electrodes 136 maylink together to form a sub-grouped regions of influence that definepeanut-like or linear shapes between two or more electrodes 136. Infurther embodiments, the ablation pattern can result in a more expansiveor contiguous pattern in which the region of influence extends alongmultiple electrodes 136 (e.g., along each strut). In still furtherembodiments, the ablation pattern may result in different regions ofinfluence depending upon the electrode activation pattern, phase angle,target temperature, pulse duration, device structure, and/or othertreatment parameters. The three-dimensional views of the ablationpatterns can be output to the display 112 and/or other user interfacesto allow the clinician to visualize the changing regions of influencebased on different durations of energy application, different electrodeactivation sequences (e.g., multiplexing), different pulse sequences,different temperature isotherms, and/or other treatment parameters. Thisinformation can be used to determine the appropriate ablation algorithmfor a patient's specific anatomy. In other embodiments, thethree-dimensional visualization of the regions of influence can be usedto illustrate the regions from which the electrodes 136 detect data whenmeasuring bioelectrical properties for anatomical mapping. In thisembodiment, the three dimensional visualization can be used to determinewhich electrode activation pattern should be used to determine thedesired properties (e.g., impedance, resistance, etc.) in the desiredarea. In certain embodiments, it may be better to use dot assessments,whereas in other embodiments it may be more appropriate to detectinformation from linear or larger contiguous regions.

In some embodiments, the mapped ablation pattern is superimposed on theanatomical mapping to identify what structures (e.g., neural structures,vessels, etc.) will be therapeutically modulated or otherwise affectedby the therapy. An image may be provided to the surgeon which includes adigital illustration of a predicted or planned neuromodulation zone inrelation to previously identified anatomical structures in a zone ofinterest. For example, the illustration may show numerous neuralstructures and, based on the predicted neuromodulation zone, identifieswhich neural structures are expected to be therapeutically modulated.The expected therapeutically modulated neural structures may be shadedto differentiate them from the non-affected neural structures. In otherembodiments, the expected therapeutically modulated neural structurescan be differentiated from the non-affected neural structures usingdifferent colors and/or other indicators. In further embodiments, thepredicted neuromodulation zone and surrounding anatomy (based onanatomical mapping) can be shown in a three dimensional view (and/orinclude different visualization features (e.g., color-coding to identifycertain anatomical structures, bioelectric properties of the targettissue, etc.). The combined predicted ablation pattern and anatomicalmapping can be output to the display 112 and/or other user interfaces toallow the clinician to select the appropriate ablation algorithm for apatient's specific anatomy.

The imaging provided by the system 100 allows the clinician to visualizethe ablation pattern before therapy and adjust the ablation pattern totarget specific anatomical structures while avoiding others to preventcollateral effects. For example, the clinician can select a treatmentpattern to avoid blood vessels, thereby reducing exposure of the vesselto the therapeutic neuromodulation energy. This reduces the risk ofdamaging or rupturing vessels and, therefore, prevents immediate orlatent bleeding. Further, the selective energy application provided bythe neural mapping reduces collateral effects of the therapeuticneuromodulation, such as tissue sloughing off during wound healing(e.g., 1-3 weeks post ablation), thereby reducing the aspiration riskassociated with the neuromodulation procedure.

The system 100 can be further configured to apply neuromodulation energy(via the electrodes 136) at specific frequencies attuned to the targetneural structure and, therefore, specifically target desired neuralstructures over non-target structures. For example, the specificneuromodulation frequencies can correspond to the frequencies identifiedas corresponding to the target structure during neural mapping. Asdescribed above, the inherent morphology and composition of theanatomical structures react differently to different frequencies. Thus,frequency-tuned neuromodulation energy tailored to a target structuredoes not have the same modulating effects on non-target structures. Morespecifically, applying the neuromodulation energy at the target-specificfrequency causes ionic agitation in the target neural structure, leadingto differentials in osmotic potentials of the targeted neural structuresand dynamic changes in neuronal membronic potentials (resulting from thedifference in intra-cellular and extra-cellular fluidic pressure). Thiscauses degeneration, possibly resulting in vacuolar degeneration and,eventually, necrosis at the target neural structure, but is not expectedto functionally affect at least some non-target structures (e.g., bloodvessels). Accordingly, the system 100 can use the neural-structurespecific frequencies to both (1) identify the locations of target neuralstructures to plan electrode ablation configurations (e.g., electrodegeometry and/or activation pattern) that specifically focus theneuromodulation on the target neural structure; and (2) apply theneuromodulation energy at the characteristic neural frequencies toselectively ablate the neural structures responsive to thecharacteristic neural frequencies. For example, the end effector 114 ofthe system 100 may selectively stimulate and/or modulate parasympatheticfibers, sympathetic fibers, sensory fibers, alpha/beta/delta fibers,C-fibers, anoxic terminals of one or more of the foregoing, insulatedover non-insulated fibers (regions with fibers), and/or other neuralstructures. In some embodiments, the system 100 may also selectivelytarget specific cells or cellular regions during anatomical mappingand/or therapeutic modulation, such as smooth muscle cells, sub-mucosalglands, goblet cells, stratified cellular regions within the nasalmucosa. Therefore, the system 100 provides highly selectiveneuromodulation therapy specific to targeted neural structures, andreduces the collateral effects of neuromodulation therapy to non-targetstructures (e.g., blood vessels).

The present disclosure provides a method of anatomical mapping andtherapeutic neuromodulation. The method includes expanding an endeffector (i.e., end effector 114) at a zone of interest (“interestzone”), such as in a portion of the nasal cavity. For example, the endeffector 114 can be expanded such that at least some of the electrodes136 are placed in contact with mucosal tissue at the interest zone. Theexpanded device can then take bioelectric measurements via theelectrodes 136 and/or other sensors to ensure that the desiredelectrodes are in proper contact with the tissue at the interest zone.In some embodiments, for example, the system 100 detects the impedanceand/or resistance across pairs of the electrodes 136 to confirm that thedesired electrodes have appropriate surface contact with the tissue andthat all of the electrodes are 136 functioning properly.

The method continues by optionally applying an electrical stimulus tothe tissue, and detecting bioelectric properties of the tissue toestablish baseline norms of the tissue. For example, the method caninclude measuring resistance, complex impedance, current, voltage, nervefiring rate, neuromagnetic field, muscular activation, and/or otherparameters that are indicative of the location and/or function of neuralstructures and/or other anatomical structures (e.g., glandularstructures, blood vessels, etc.). In some embodiments, the electrodes136 send one or more stimulation signals (e.g., pulsed signals orconstant signals) to the interest zone to stimulate neural activity andinitiate action potentials. The stimulation signal can have a frequencyattuned to a specific target structure (e.g., a specific neuralstructure, a glandular structure, a vessel) that allows foridentification of the location of the specific target structure. Thespecific frequency of the stimulation signal is a function of the hostpermeability and, therefore, applying the unique frequency alters thetissue attenuation and the depth into the tissue the RF energy willpenetrate. For example, lower frequencies typically penetrate deeperinto the tissue than higher frequencies.

Pairs of the non-stimulating electrodes 136 of the end effector 114 canthen detect one or more bioelectric properties of the tissue that occurin response to the stimulus, such as impedance or resistance. Forexample, an array of electrodes (e.g., the electrodes 136) can beselectively paired together in a desired pattern (e.g., multiplexing theelectrodes 136) to detect the bioelectric properties at desired depthsand/or across desired regions to provide a high level of spatialawareness at the interest zone. In certain embodiments, the electrodes136 can be paired together in a time-sequenced manner according to analgorithm (e.g., provided by the mapping/evaluation/feedback algorithms110). In various embodiments, stimuli can be injected into the tissue attwo or more different frequencies, and the resultant bioelectricresponses (e.g., action potentials) in response to each of the injectedfrequencies can be detected via various pairs of the electrodes 136. Forexample, an anatomical or neural mapping algorithm can cause the endeffector 114 to deliver pulsed RF energy at specific frequencies betweendifferent pairs of the electrodes 136 and the resultant bioelectricresponse can be recorded in a time sequenced rotation until the desiredinterest zone is adequately mapped (i.e., “multiplexing”). For example,the end effector 114 can deliver stimulation energy at a first frequencyvia adjacent pairs of the electrodes 136 for a predetermined time period(e.g., 1-50 milliseconds), and the resultant bioelectric activity (e.g.,resistance) can be detected via one or more other pairs of electrodes136 (e.g., spaced apart from each other to reach varying depths withinthe tissue). The end effector 114 can then apply stimulation energy at asecond frequency different from the first frequency, and the resultantbioelectric activity can be detected via the other electrodes. This cancontinue when the interest zone has been adequately mapped at thedesired frequencies. As described in further detail below, in someembodiments the baseline tissue bioelectric properties (e.g., nervefiring rate) are detected using static detection methods (without theinjection of a stimulation signal).

After detecting the baseline bioelectric properties, the information canbe used to map anatomical structures and/or functions at the interestzone. For example, the bioelectric properties detected by the electrodes136 can be amazed via the mapping/evaluation/feedback algorithms 110,and an anatomical map can be output to a user via the display 112. Insome embodiments, complex impedance, dielectric, or resistancemeasurements can be used to map parasympathetic nerves and, optionally,identify neural structures in a diseased state of hyperactivity. Thebioelectric properties can also be used to map other non-targetstructures and the general anatomy, such as blood vessels, bone, and/orglandular structures. The anatomical locations can be provided to a user(e.g., on the display 112) as a two-dimensional map (e.g., illustratingrelative intensities, illustrating specific sites of potential targetstructures) and/or as a three-dimensional image. This information can beused to differentiate structures on a submicron, cellular level andidentify very specific target structures (e.g., hyperactiveparasympathetic nerves). The method can also predict the ablationpatterns of the end effector 114 based on different electrodeneuromodulation protocol and, optionally, superimpose the predictedneuromodulation patterns onto the mapped anatomy to indicate to the userwhich anatomical structures will be affected by a specificneuromodulation protocol. For example, when the predictedneuromodulation pattern is displayed in relation to the mapped anatomy,a clinician can determine whether target structures will beappropriately ablated and whether non-target structures (e.g., bloodvessels) will be undesirably exposed to the therapeutic neuromodulationenergy. Thus, the method can be used for planning neuromodulationtherapy to locate very specific target structures, avoid non-targetstructures, and select electrode neuromodulation protocols.

Once the target structure is located and a desired electrodeneuromodulation protocol has been selected, the method continues byapplying therapeutic neuromodulation to the target structure. Theneuromodulation energy can be applied to the tissue in a highly targetedmanner that forms micro-lesions to selectively modulate the targetstructure, while avoiding non-targeted blood vessels and allowing thesurrounding tissue structure to remain healthy for effective woundhealing. In some embodiments, the neuromodulation energy can be appliedin a pulsed manner, allowing the tissue to cool between modulationpulses to ensure appropriate modulation without undesirably affectingnon-target tissue. In some embodiments, the neuromodulation algorithmcan deliver pulsed RF energy between different pairs of the electrodes136 in a time sequenced rotation until neuromodulation is predicted tobe complete (i.e., “multiplexing”). For example, the end effector 114can deliver neuromodulation energy (e.g., having a power of 5-10 W(e.g., 7 W, 8 W, 9 W) and a current of about 50-100 mA) via adjacentpairs of the electrodes 136 until at least one of the followingconditions is met: (a) load resistance reaches a predefined maximumresistance (e.g., 350Ω); (b) a thermocouple temperature associated withthe electrode pair reaches a predefined maximum temperature (e.g., 80°C.); or (c) a predetermined time period has elapsed (e.g., 10 seconds).After the predetermined conditions are met, the end effector 114 canmove to the next pair of electrodes in the sequence, and theneuromodulation algorithm can terminate when all of the load resistancesof the individual pairs of electrodes is at or above a predeterminedthreshold (e.g., 100Ω). In various embodiments, the RF energy can beapplied at a predetermined frequency (e.g., 450-500 kHz) and is expectedto initiate ionic agitation of the specific target structure, whileavoiding functional disruption of non-target structures.

During and/or after neuromodulation therapy, the method continues bydetecting and, optionally, mapping the post-therapy bioelectricproperties of the target site. This can be performed in a similar manneras described above. The post-therapy evaluation can indicate if thetarget structures (e.g., hyperactive parasympathetic nerves) wereadequately modulated or ablated. If the target structures are notadequately modulated (i.e., if neural activity is still detected in thetarget structure and/or the neural activity has not decreased), themethod can continue by again applying therapeutic neuromodulation to thetarget. If the target structures were adequately ablated, theneuromodulation procedure can be completed.

Detection of Anatomical Structures and Function

Various embodiments of the present technology can include features thatmeasure bio-electric, dielectric, and/or other properties of tissue attarget sites to determine the presence, location, and/or activity ofneural structures and other anatomical structures and, optionally, mapthe locations of the detected neural structures and/or other anatomicalstructures. For example, the present technology can be used to detectglandular structures and, optionally, their mucoserous functions and/orother functions. The present technology can also be configured to detectvascular structures (e.g., arteries) and, optionally, their arterialfunctions, volumetric pressures, and/or other functions. The mappingfeatures discussed below can be incorporated into any the system 100and/or any other devices disclosed herein to provide an accuratedepiction of nerves at the target site.

Neural and/or anatomical detection can occur (a) before the applicationof a therapeutic neuromodulation energy to determine the presence orlocation of neural structures and other anatomical structures (e.g.,blood vessels, glands, etc.) at the target site and/or record baselinelevels of neural activity; (b) during therapeutic neuromodulation todetermine the real-time effect of the energy application on the neuralfibers at the treatment site; and/or (c) after therapeuticneuromodulation to confirm the efficacy of the treatment on the targetedstructures (e.g., nerves glands, etc.). This allows for theidentification of very specific anatomical structures (even to themicro-scale or cellular level) and, therefore, provides for highlytargeted neuromodulation. This enhances the efficacy and efficiency ofthe neuromodulation therapy. In addition, the anatomical mapping reducesthe collateral effects of neuromodulation therapy to non-target sites.Accordingly, the targeted neuromodulation inhibits damage or rupture ofblood vessels (i.e., inhibits undesired bleeding) and collateral damageto tissue that may be of concern during wound healing (e.g., when damagetissue sloughs off of the wall of the nasal wall).

In certain embodiments, the systems disclosed herein can use bioelectricmeasurements, such as impedance, resistance, voltage, current density,and/or other parameters (e.g., temperature) to determine the anatomy, inparticular the neural, glandular, and vascular anatomy, at the targetsite. The bioelectric properties can be detected after the transmissionof a stimulus (e.g., an electrical stimulus, such as RF energy deliveredvia the electrodes 136; i.e., “dynamic” detection) and/or without thetransmission of a stimulus (i.e., “static” detection).

Dynamic measurements include various embodiments to excite and/or detectprimary or secondary effects of neural activation and/or propagation.Such dynamic embodiments involve the heightened states of neuralactivation and propagation and use this dynamic measurement for nervelocation and functional identification relative to the neighboringtissue types. For example, a method of dynamic detection can include:(1) delivering stimulation energy to a treatment site via a treatmentdevice (e.g., the end effector 114) to excite parasympathetic nerves atthe treatment site; (2) measuring one or more physiological parameters(e.g., resistance, impedance, etc.) at the treatment site via ameasuring/sensing array of the treatment device (e.g., the electrodes136); (4) based on the measurements, identifying the relative presenceand position of parasympathetic nerves at the treatment site; and (5)delivering ablation energy to the identified parasympathetic nerves toblock the detected para-sympathetic nerves.

Static measurements include various embodiments associated with specificnative properties of the stratified or cellular composition at or nearthe treatment site. The static embodiments are directed to inherentbiologic and electrical properties of tissue types at or near thetreatment site, the stratified or cellular compositions at or near thetreatment site, and contrasting both foregoing measurements with tissuetypes adjacent the treatment site (and that are not targeted forneuromodulation). This information can be used to localize specifictargets (e.g., parasympathetic fibers) and non-targets (e.g., vessels,sensory nerves, etc.). For example, a method of static detection caninclude: (1) before ablation, utilizing a measuring/sensing array of atreatment device (e.g., the electrodes 136) to determine one or morebaseline physiological parameters; (2) geometrically identifyinginherent tissue properties within a region of interest based on themeasured physiological parameters (e.g., resistance, impedance, etc.);(3) delivering ablation energy to one or more nerves within the regionof via treatment device interest; (4) during the delivery of theablation energy, determining one or more mid-procedure physiologicalparameters via the measuring/sensing array; and (5) after the deliveryof ablation energy, determining one or more post-procedure physiologicalparameters via the measurement/sensing array to determine theeffectiveness of the delivery of the ablation energy on blocking thenerves that received the ablation energy.

After the initial static and/or dynamic detection of bioelectricproperties, the location of anatomical features can be used to determinewhere the treatment site(s) should be with respect to various anatomicalstructures for therapeutically effective neuromodulation of the targetedparasympathetic nasal nerves. The bioelectric and other physiologicalproperties described herein can be detected via electrodes (e.g., theelectrodes 136 of the end effector 114), and the electrode pairings on adevice (e.g., end effector 114) can be selected to obtain thebioelectric data at specific zones or regions and at specific depths ofthe targeted regions. The specific properties detected at or surroundingtarget neuromodulation sites and associated methods for obtaining theseproperties are described below. These specific detection and mappingmethods discussed below are described with reference to the system 100,although the methods can be implemented on other suitable systems anddevices that provide for anatomical identification, anatomical mappingand/or neuromodulation therapy.

Neural Identification and Mapping

In many neuromodulation procedures, it is beneficial to identify theportions of the nerves that fall within a zone and/or region ofinfluence (referred to as the “interest zone”) of the energy deliveredby a neuromodulation device 102, as well as the relativethree-dimensional position of the neural structures relative to theneuromodulation device 102. Characterizing the portions of the neuralstructures within the interest zone and/or determining the relativepositions of the neural structures within the interest zone enables theclinician to (1) selectively activate target neural structures overnon-target structures (e.g., blood vessels), and (2) sub-select specifictargeted neural structures (e.g., parasympathetic nerves) overnon-target neural structures (e.g., sensory nerves, subgroups of neuralstructures, neural structures having certain compositions ormorphologies). The target structures (e.g., parasympathetic nerves) andnon-target structures (e.g., blood vessels, sensory nerves, etc.) can beidentified based on the inherent signatures of specific structures,which are defined by the unique morphological compositions of thestructures and the bioelectrical properties associated with thesemorphological compositions. For example, unique, discrete frequenciescan be associated with morphological compositions and, therefore, beused to identify certain structures. The target and non-targetstructures can also be identified based on relative bioelectricalactivation of the structures to sub-select specific neuronal structures.Further, target and non-target structures can be identified by thediffering detected responses of the structures to a tailored injectedstimuli. For example, the systems described herein can detect themagnitude of response of structures and the difference in the responsesof anatomical structures with respect to differing stimuli (e.g.,stimuli injected at different frequencies).

At least for purposes of this disclosure, a nerve can include thefollowing portions that are defined based on their respectiveorientations relative to the interest zone: terminating neuralstructures (e.g., terminating axonal structures), branching neuralstructures (e.g., branching axonal structures), and travelling neuralstructures (e.g., travelling axonal structures). For example,terminating neural structures enter the zone but do not exit. As such,terminating neural structures are terminal points for neuronal signalingand activation. Branching neural structures are nerves that enter theinterest zone and increase number of nerves exiting the interest zone.Branching neural structures are typically associated with a reduction inrelative geometry of nerve bundle. Travelling neural structures arenerves that enter the interest zone and exit the zone with nosubstantially no change in geometry or numerical value.

The system 100 can be used to detect voltage, current, compleximpedance, resistance, permittivity, and/or conductivity, which are tiedto the compound action potentials of nerves, to determine and/or map therelative positions and proportionalities of nerves in the interest zone.Neuronal cross-sectional area (“CSA”) is expected to be due to theincrease in axonic structures. Each axon is a standard size. Largernerves (in cross-sectional dimension) have a larger number of axons thannerves having smaller cross-sectional dimensions. The compound actionresponses from the larger nerves, in both static and dynamicassessments, are greater than smaller nerves. This is at least in partbecause the compound action potential is the cumulative action responsefrom each of the axons. When using static analysis, for example, thesystem 100 can directly measure and map impedance or resistance ofnerves and, based on the determined impedance or resistance, determinethe location of nerves and/or relative size of the nerves. In dynamicanalysis, the system 100 can be used to apply a stimulus to the interestzone and detect the dynamic response of the neural structures to thestimulus. Using this information, the system 100 can determine and/ormap impedance or resistance in the interest zone to provide informationrelated to the neural positions or relative nerve sizes. Neuralimpedance mapping can be illustrated by showing the varying compleximpedance levels at a specific location at differing cross-sectionaldepths. In other embodiments, neural impedance or resistance can bemapped in a three-dimensional display.

Identifying the portions and/or relative positions of the nerves withinthe interest zone can inform and/or guide selection of one or moretreatment parameters (e.g., electrode ablation patterns, electrodeactivation plans, etc.) of the system 100 for improving treatmentefficiency and efficacy. For example, during neural monitoring andmapping, the system 100 can identify the directionality of the nervesbased at least in part on the length of the neural structure extendingalong the interest zone, relative sizing of the neural structures,and/or the direction of the action potentials. This information can thenbe used by the system 100 or the clinician to automatically or manuallyadjust treatment parameters (e.g., selective electrode activation,bipolar and/or multipolar activation, and/or electrode positioning) totarget specific nerves or regions of nerves. For example, the system 100can selectively activate specific electrodes 136, electrode combinations(e.g., asymmetric or symmetric), and/or adjust the bi-polar ormulti-polar electrode configuration. In some embodiments, the system 100can adjust or select the waveform, phase angle, and/or other energydelivery parameters based on the nerve portion/position mapping and/orthe nerve proportionality mapping. In some embodiments, structure and/orproperties of the electrodes 136 themselves (e.g., material, surfaceroughening, coatings, cross-sectional area, perimeter, penetrating,penetration depth, surface-mounted, etc.) may be selected based on thenerve portion and proportionality mapping.

In various embodiments, treatment parameters and/or energy deliveryparameters can be adjusted to target on-axis or near axis travellingneural structures and/or avoid the activation of traveling neuralstructures that are at least generally perpendicular to the end effector114. Greater portions of the on-axis or near axis travelling neuralstructures are exposed and susceptible to the neuromodulation energyprovided by the end effector 114 than a perpendicular travelling neuralstructure, which may only be exposed to therapeutic energy at a discretecross-section. Therefore, the end effector 114 is more likely to have agreater effect on the on-axis or near axis travelling neural structures.The identification of the neural structure positions (e.g., via compleximpedance or resistance mapping) can also allow targeted energy deliveryto travelling neural structures rather than branching neural structures(typically downstream of the travelling neural structures) because thetravelling neural structures are closer to the nerve origin and,therefore, more of the nerve is affected by therapeutic neuromodulation,thereby resulting in a more efficient treatment and/or a higher efficacyof treatment. Similarly, the identification of neural structurepositions can be used to target travelling and branching neuralstructures over terminal neural structures. In some embodiments, thetreatment parameters can be adjusted based on the detected neuralpositions to provide a selective regional effect. For example, aclinician can target downstream portions of the neural structures ifonly wanting to influence partial effects on very specific anatomicalstructures or positions.

In various embodiments, neural locations and/or relative positions ofnerves can be determined by detecting the nerve-firing voltage and/orcurrent over time. An array of the electrodes 136 can be positioned incontact with tissue at the interest zone, and the electrodes 136 canmeasure the voltage and/or current associated with nerve-firing. Thisinformation can optionally be mapped (e.g., on a display 112) toidentify the location of nerves in a hyper state (i.e., excessiveparasympathetic tone). Rhinitis is at least in part the result ofover-firing nerves because this hyper state drives the hyper-mucosalproduction and hyper-mucosal secretion. Therefore, detection of nervefiring rate via voltage and current measurements can be used to locatethe portions of the interest region that include hyper-parasympatheticneural function (i.e., nerves in the diseased state). This allows theclinician to locate specific nerves (i.e., nerves with excessiveparasympathetic tone) before neuromodulation therapy, rather than simplytargeting all parasympathetic nerves (including non-diseased stateparasympathetic nerves) to ensure that the correct tissue is treatedduring neuromodulation therapy. Further, nerve firing rate can bedetected during or after neuromodulation therapy so that the cliniciancan monitor changes in nerve firing rate to validate treatment efficacy.For example, recording decreases or elimination of nerve firing rateafter neuromodulation therapy can indicate that the therapy waseffective in therapeutically treating the hyper/diseased nerves.

In various embodiments, the system 100 can detect neural activity usingdynamic activation by injecting a stimulus signal (i.e., a signal thattemporarily activates nerves) via one or more of the electrodes 136 toinduce an action potential, and other pairs of electrodes 136 can detectbioelectric properties of the neural response. Detecting neuralstructures using dynamic activation involves detecting the locations ofaction potentials within the interest zone by measuring the dischargerate in neurons and the associated processes. The ability to numericallymeasure, profile, map, and/or image fast neuronal depolarization forgenerating an accurate index of activity is a factor in measuring therate of discharge in neurons and their processes. The action potentialcauses a rapid increase in the voltage across nerve fiber and theelectrical impulse then spreads along the fiber. As an action potentialoccurs, the conductance of a neural cell membrane changes, becomingabout 40 times larger than it is when the cell is at rest. During theaction potential or neuronal depolarization, the membrane resistancediminishes by about 80 times, thereby allowing an applied current toenter the intracellular space as well. Over a population of neurons,this leads to a net decrease in the resistance during coherent neuronalactivity, such as chronic para-sympathetic responses, as theintracellular space will provide additional conductive ions. Themagnitude of such fast changes has been estimated to have localresistivity changes with recording near DC is 2.8-3.7% for peripheralnerve bundles (e.g., including the nerves in the nasal cavity).

Detecting neural structures using dynamic activation includes detectingthe locations of action potentials within the interest zone by measuringthe discharge rate in neurons and the associated processes. The basis ofeach this discharge is the action potential, during which there is adepolarization of the neuronal membrane of up to 110 mV or more, lastingapproximately 2 milliseconds, and due to the transfer of micromolarquantities of ions (e.g., sodium and potassium) across the cellularmembrane. The complex impedance or resistance change due to the neuronalmembrane falls from 1000 to 25 Ωcm. The introduction of a stimulus andsubsequent measurement of the neural response can attenuate noise andimprove signal to noise ratios to precisely focus on the response regionto improve neural detection, measurement, and mapping.

In some embodiments, the difference in measurements of physiologicalparameters (e.g., complex impedance, resistance, voltage) over time,which can reduce errors, can be used to create a neural profiles,spectrums, or maps. For example, the sensitivity of the system 100 canbe improved because this process provides repeated averaging to astimulus. As a result, the mapping function outputs can be a unit-lessratio between the reference and test collated data at a single frequencyand/or multiple frequencies and/or multiple amplitudes. Additionalconsiderations may include multiple frequency evaluation methods thatconsequently expand the parameter assessments, such as resistivity,admittivity, center frequency, or ratio of extra- to intracellularresistivity.

In some embodiments, the system 100 may also be configured to indirectlymeasure the electrical activity of neural structures to quantify themetabolic recovery processes that accompany action potential activityand act to restore ionic gradients to normal. These are related to anaccumulation of ions in the extracellular space. The indirectmeasurement of electrical activity can be approximately a thousand timeslarger (in the order of millimolar), and thus are easier to measure andcan enhance the accuracy of the measured electrical properties used togenerate the neural maps.

The system 100 can perform dynamic neural detection by detectingnerve-firing voltage and/or current and, optionally, nerve firing rateover time, in response to an external stimulation of the nerves. Forexample, an array of the electrodes 136 can be positioned in contactwith tissue at the interest zone, one or more of the electrodes 136 canbe activated to inject a signal into the tissue that stimulates thenerves, and other electrodes 136 of the electrode array can measure theneural voltage and/or current due to nerve firing in response to thestimulus. This information can optionally be mapped (e.g., on a display112) to identify the location of nerves and, in certain embodiments,identify parasympathetic nerves in a hyper state (e.g., indicative ofRhinitis or other diseased state). The dynamic detection of neuralactivity (voltage, current, firing rate, etc.) can be performed beforeneuromodulation therapy to detect target nerve locations to select thetarget site and treatment parameters to ensure that the correct tissueis treated during neuromodulation therapy. Further, dynamic detection ofneural activity can be performed during or after neuromodulation therapyto allow the clinician to monitor changes in neural activity to validatetreatment efficacy. For example, recording decreases or elimination ofneural activity after neuromodulation therapy can indicate that thetherapy was effective in therapeutically treating the hyper/diseasednerves.

In some embodiments, a stimulating signal can be delivered to thevicinity of the targeted nerve via one or more penetrating electrodes(e.g., microneedles that penetrate tissue) associated with the endeffector 114 and/or a separate device. The stimulating signal generatesan action potential, which causes smooth muscle cells or other cells tocontract. The location and strength of this contraction can be detectedvia the penetrating electrode(s) and, thereby, indicate to the clinicianthe distance to the nerve and/or the location of the nerve relative tothe stimulating needle electrode. In some embodiments, the stimulatingelectrical signal may have a voltage of typically 1-2 mA or greater anda pulse width of typically 100-200 microseconds or greater. Shorterpulses of stimulation result in better discrimination of the detectedcontraction, but may require more current. The greater the distancebetween the electrode and the targeted nerve, the more energy isrequired to stimulate. The stimulation and detection of contractionstrength and/or location enables identification of how close or far theelectrodes are from the nerve, and therefore can be used to localize thenerve spatially. In some embodiments, varying pulse widths may be usedto measure the distance to the nerve. As the needle becomes closer tothe nerve, the pulse duration required to elicit a response becomes lessand less.

To localize nerves via muscle contraction detection, the system 100 canvary pulse-width or amplitude to vary the energy(Energy=pulse−width*amplitude) of the stimulus delivered to the tissuevia the penetrating electrode(s). By varying the stimulus energy andmonitoring muscle contraction via the penetrating electrodes and/orother type of sensor, the system 100 can estimate the distance to thenerve. If a large amount of energy is required to stimulate thenerve/contract the muscle, the stimulating/penetrating electrode is farfrom the nerve. As the stimulating/penetrating electrode, moves closerto the nerve, the amount of energy required to induce muscle contractionwill drop. For example, an array of penetrating electrodes can bepositioned in the tissue at the interest zone and one or more of theelectrodes can be activated to apply stimulus at different energy levelsuntil they induce muscle contraction. Using an iterative process,localize the nerve (e.g., via the mapping/evaluation/feedback algorithm110).

In some embodiments, the system 100 can measure the muscular activationfrom the nerve stimulus (e.g., via the electrodes 136) to determineneural positioning for neural mapping, without the use of penetratingelectrodes. In this embodiment, the treatment device targets the smoothmuscle cells' varicosities surrounding the submucosal glands and thevascular supply, and then the compound muscle action potential. This canbe used to summate voltage response from the individual muscle fiberaction potentials. The shortest latency is the time from stimulusartifact to onset of the response. The corresponding amplitude ismeasured from baseline to negative peak and measured in millivolts (mV).Nerve latencies (mean±SD) in adults typically range about 2-6milliseconds, and more typically from about 3.4±0.8 to about 4.0±0.5milliseconds. A comparative assessment may then be made which comparesthe outputs at each time interval (especially pre- and post-energydelivery) in addition to a group evaluation using the alternative nasalcavity. This is expected to provide an accurate assessment of theabsolute value of the performance of the neural functioning becausemuscular action/activation may be used to infer neural action/activationand muscle action/activation is a secondary effect or by-product whilstthe neural function is the absolute performance measure.

In some embodiments, the system 100 can record a neuromagnetic fieldoutside of the nerves to determine the internal current of the nerveswithout physical disruption of the nerve membrane. Without being boundby theory, the contribution to the magnetic field from the currentinside the membrane is two orders of magnitude larger than that from theexternal current, and that the contribution from current within themembrane is substantially negligible. Electrical stimulation of thenerve in tandem with measurements of the magnetic compound action fields(“CAFs”) can yield sequential positions of the current dipoles such thatthe location of the conduction change can be estimated (e.g., via theleast-squares method). Visual representation (e.g., via the display 112)using magnetic contour maps can show normal or non-normal neuralcharacteristics (e.g., normal can be equated with a characteristicquadrupolar pattern propagating along the nerve), and therefore indicatewhich nerves are in a diseases, hyperactive state and suitable targetsfor neuromodulation.

During magnetic field detection, an array of the electrodes 136 can bepositioned in contact with tissue at the interest zone and, optionally,one or more of the electrodes 136 can be activated to inject anelectrical stimulus into the tissue. As the nerves in the interest zonefire (either in response to a stimulus or in the absence of it), thenerve generates a magnetic field (e.g., similar to a current carryingwire), and therefore changing magnetic fields are indicative of thenerve nerve-firing rate. The changing magnetic field caused by neuralfiring can induce a current detected by nearby sensor wire (e.g., thesensor 314) and/or wires associated with the nearby electrodes 136. Bymeasuring this current, the magnetic field strength can be determined.The magnetic fields can optionally be mapped (e.g., on a display 112) toidentify the location of nerves and select target nerves (nerves withexcessive parasympathetic tone) before neuromodulation therapy to ensurethat the desired nerves are treated during neuromodulation therapy.Further, the magnetic field information can be used during or afterneuromodulation therapy so that the clinician can monitor changes innerve firing rate to validate treatment efficacy.

In other embodiments, the neuromagnetic field is measured with a HallProbe or other suitable device, which can be integrated into the endeffector 114 and/or part of a separate device delivered to the interestzone. Alternatively, rather than measuring the voltage in the secondwire, the changing magnetic field can be measured in the original wire(i.e. the nerve) using a Hall probe. A current going through the Hallprobe will be deflected in the semi-conductor. This will cause a voltagedifference between the top and bottom portions, which can be measured.In some aspects of this embodiments, three orthogonal planes areutilized.

In some embodiments, the system 100 can be used to induce electromotiveforce (“EMF”) in a wire (i.e., a frequency-selective circuit, such as atunable/LC circuit) that is tunable to resonant frequency of a nerve. Inthis embodiment, the nerve can be considered to be a current carryingwire, and the firing action potential is a changing voltage. This causesa changing current which, in turn, causes a changing magnetic flux(i.e., the magnetic field that is perpendicular to the wire). UnderFaraday's Law of Induction/Faraday's Principle, the changing magneticflux induces EMF (including a changing voltage) in a nearby sensor wire(e.g., integrated into the end effector 114, the sensor 314, and/orother structure), and the changing voltage can be measured via thesystem 100.

In further embodiments, the sensor wire (e.g., the sensor 314) is aninductor and, therefore, provides an increase of the magnetic linkagebetween the nerve (i.e., first wire) and the sensor wire (i.e., secondwire), with more turns for increasing effect. (e.g., V2,rms=V1,rms(N2/N1)). Due to the changing magnetic field, a voltage is induced inthe sensor wire, and this voltage can be measured and used to estimatecurrent changes in the nerve. Certain materials can be selected toenhance the efficiency of the EMF detection. For example, the sensorwire can include a soft iron core or other high permeability materialfor the inductor.

During induced EMF detection, the end effector 114 and/or other deviceincluding a sensor wire is positioned in contact with tissue at theinterest zone and, optionally, one or more of the electrodes 136 can beactivated to inject an electrical stimulus into the tissue. As thenerves in the interest zone fire (either in response to a stimulus or inthe absence of it), the nerve generates a magnetic field (e.g., similarto a current carrying wire) that induces a current in the sensor wire(e.g., the sensor 314). This information can be used to determine neurallocation and/or map the nerves (e.g., on a display 112) to identify thelocation of nerves and select target nerves (nerves with excessiveparasympathetic tone) before neuromodulation therapy to ensure that thedesired nerves are treated during neuromodulation therapy. EMFinformation can also be used during or after neuromodulation therapy sothat the clinician can monitor changes in nerve firing rate to validatetreatment efficacy.

In some embodiments, the system 100 can detect magnetic fields and/orEMF generated at a selected frequency that corresponds to a particulartype of nerve. The frequency and, by extension, the associated nervetype of the detected signal can be selected based on an externalresonant circuit. Resonance occurs on the external circuit when it ismatched to the frequency of the magnetic field of the particular nervetype and that nerve is firing. In manner, the system 100 can be used tolocate a particular sub-group/type of nerves.

In some embodiments, the system 100 can include a variable capacitorfrequency-selective circuit to identify the location and/or map specificnerves (e.g., parasympathetic nerve, sensory nerve, nerve fiber type,nerve subgroup, etc.). The variable capacitor frequency-selectivecircuit can be defined by the sensor 314 and/or other feature of the endeffector 114. Nerves have different resonant frequencies based on theirfunction and structure. Accordingly, the system 100 can include atunable LC circuit with a variable capacitor (C) and/or variableinductor (L) that can be selectively tuned to the resonant frequency ofdesired nerve types. This allows for the detection of neural activityonly associated with the selected nerve type and its associated resonantfrequency. Tuning can be achieved by moving the core in and out of theinductor. For example, tunable LC circuits can tune the inductor by: (i)changing the number of coils around the core; (ii) changing thecross-sectional area of the coils around the core; (iii) changing thelength of the coil; and/or (iv) changing the permeability of the corematerial (e.g., changing from air to a core material). Systems includingsuch a tunable LC circuit provide a high degree of dissemination anddifferentiation not only as to the activation of a nerve signal, butalso with respect to the nerve type that is activated and the frequencyat which the nerve is firing.

Anatomical Mapping

In various embodiments, the system 100 is further configured to provideminimally-invasive anatomical mapping that uses focused energycurrent/voltage stimuli from a spatially localized source (e.g., theelectrodes 136) to cause a change in the conductivity of the of thetissue at the interest zone and detect resultant biopotential and/orbioelectrical measurements (e.g., via the electrodes 136). The currentdensity in the tissue changes in response to changes of voltage appliedby the electrodes 136, which creates a change in the electric currentthat can be measured with the end effector 114 and/or other portions ofthe system 100. The results of the bioelectrical and/or biopotentialmeasurements can be used to predict or estimate relative absorptionprofilometry to predict or estimate the tissue structures in theinterest zone. More specifically, each cellular construct has uniqueconductivity and absorption profiles that can be indicative of a type oftissue or structure, such as bone, soft tissue, vessels, nerves, typesof nerves, and/or certain neural structures. For example, differentfrequencies decay differently through different types of tissue.Accordingly, by detecting the absorption current in a region, the system100 can determine the underlying structure and, in some instances, to asub-microscale, cellular level that allows for highly specialized targetlocalization and mapping. This highly specific target identification andmapping enhances the efficacy and efficiency of neuromodulation therapy,while also enhancing the safety profile of the system 100 to reducecollateral effects on non-target structures.

To detect electrical and dielectric tissue properties (e.g., resistance,complex impedance, conductivity, and/or, permittivity as a function offrequency), the electrodes 136 and/or another electrode array is placedon tissue at an interest region, and an internal or external source(e.g., the generator 106) applies stimuli (current/voltage) to thetissue. The electrical properties of the tissue between the source andthe receiver electrodes 136 are measured, as well as the current and/orvoltage at the individual receiver electrodes 136. These individualmeasurements can then be converted into an electrical map/image/profileof the tissue and visualized for the user on the display 112 to identifyanatomical features of interest and, in certain embodiments, thelocation of firing nerves. For example, the anatomical mapping can beprovided as a color-coded or gray-scale three-dimensional ortwo-dimensional map showing differing intensities of certain bioelectricproperties (e.g., resistance, impedance, etc.), or the information canbe processed to map the actual anatomical structures for the clinician.This information can also be used during neuromodulation therapy tomonitor treatment progression with respect to the anatomy, and afterneuromodulation therapy to validate successful treatment. In addition,the anatomical mapping provided by the bioelectrical and/or biopotentialmeasurements can be used to track the changes to non-target tissue(e.g., vessels) due to neuromodulation therapy to avoid negativecollateral effects. For example, a clinician can identify when thetherapy begins to ligate a vessel and/or damage tissue, and modify thetherapy to avoid bleeding, detrimental tissue ablation, and/or othernegative collateral effects.

Furthermore, the threshold frequency of electric current used toidentify specific targets can subsequently be used when applyingtherapeutic neuromodulation energy. For example, the neuromodulationenergy can be applied at the specific threshold frequencies of electriccurrent that are target neuronal-specific and differentiated from othernon-targets (e.g., blood vessels, non-target nerves, etc.). Applyingablation energy at the target-specific frequency results in an electricfield that creates ionic agitation in the target neural structure, whichleads to differentials in osmotic potentials of the targeted neuralstructures. These osmotic potential differentials cause dynamic changesin neuronal membronic potentials (resulting from the difference inintra-cellular and extra-cellular fluidic pressure) that lead tovacuolar degeneration of the targeted neural structures and, eventually,necrosis. Using the highly targeted threshold neuromodulation energy toinitiate the degeneration allows the system 100 to delivery therapeuticneuromodulation to the specific target, while surrounding blood vesselsand other non-target structures are functionally maintained.

In some embodiments, the system 100 can further be configured to detectbioelectrical properties of tissue by non-invasively recordingresistance changes during neuronal depolarization to map neural activitywith electrical impedance, resistance, bio-impedance, conductivity,permittivity, and/or other bioelectrical measurements. Without beingbound by theory, when a nerve depolarizes, the cell membrane resistancedecreases (e.g., by approximately 80×) so that current will pass throughopen ion channels and into the intracellular space. Otherwise thecurrent remains in the extracellular space. For non-invasive resistancemeasurements, tissue can be stimulated by applying a current of lessthan 100 Hz, such as applying a constant current square wave at 1 Hzwith an amplitude less than 25% (e.g., 10%) of the threshold forstimulating neuronal activity, and thereby preventing or reducing thelikelihood that the current does not cross into the intracellular spaceor stimulating at 2 Hz. In either case, the resistance and/or compleximpedance is recorded by recording the voltage changes. A compleximpedance or resistance map or profile of the area can then begenerated.

For impedance/conductivity/permittivity detection, the electrodes 136and/or another electrode array are placed on tissue at an interestregion, and an internal or external source (e.g., the generator 106)applies stimuli to the tissue, and the current and/or voltage at theindividual receiver electrodes 136 is measured. The stimuli can beapplied at different frequencies to isolate different types of nerves.These individual measurements can then be converted into an electricalmap/image/profile of the tissue and visualized for the user on thedisplay 112 to identify anatomical features of interest. The neuralmapping can also be used during neuromodulation therapy to selectspecific nerves for therapy, monitor treatment progression with respectto the nerves and other anatomy, and validate successful treatment.

In some embodiments of the neural and/or anatomical detection methodsdescribed above, the procedure can include comparing the mid-procedurephysiological parameter(s) to the baseline physiological parameter(s)and/or other, previously-acquired mid-procedure physiologicalparameter(s) (within the same energy delivery phase). Such a comparisoncan be used to analyze state changes in the treated tissue. Themid-procedure physiological parameter(s) may also be compared to one ormore predetermined thresholds, for example, to indicate when to stopdelivering treatment energy. In some embodiments of the presenttechnology, the measured baseline, mid-, and post-procedure parametersinclude a complex impedance. In some embodiments of the presenttechnology, the post-procedure physiological parameters are measuredafter a pre-determined time period to allow the dissipation of theelectric field effects (ionic agitation and/or thermal thresholds), thusfacilitating accurate assessment of the treatment.

In some embodiments, the anatomical mapping methods described above canbe used to differentiate the depth of soft tissues within the nasalmucosa. The depth of mucosa on the turbinates is great whilst the depthoff the turbinate is shallow and, therefore, identifying the tissuedepth in the present technology also identifies positions within thenasal mucosa and where precisely to target. Further, by providing themicro-scale spatial impedance mapping of epithelial tissues as describedabove, the inherent unique signatures of stratified layers or cellularbodies can be used as identifying the region of interest. For example,different regions have larger or small populations of specificstructures, such as submucosal glands, so target regions can beidentified via the identification of these structures.

In some embodiments, the system 100 includes additional features thatcan be used to detect anatomical structures and map anatomical features.For example, the system 100 can include an ultrasound probe foridentification of neural structures and/or other anatomical structures.Higher frequency ultrasound provides higher resolution, but less depthof penetration. Accordingly, the frequency can be varied to achieve theappropriate depth and resolution for neural/anatomical localization.Functional identification may rely on the spatial pulse length (“SPL”)(wavelength multiplied by number of cycles in a pulse). Axial resolution(SPL/2) may also be determined to locate nerves.

In some embodiments, the system 100 can further be configured to emitstimuli with selective parameters that suppress rather than fullystimulate neural activity. for example, in embodiments where thestrength-duration relationship for extracellular neural stimulation isselected and controlled, a state exists where the extracellular currentcan hyperpolarize cells, resulting in suppression rather thanstimulation spiking behavior (i.e., a full action potential is notachieved). Both models of ion channels, HH and RGC, suggest that it ispossible to hyperpolarize cells with appropriately designed burstextracellular stimuli, rather than extending the stimuli. Thisphenomenon could be used to suppress rather than stimulate neuralactivity during any of the embodiments of neural detection and/ormodulation described herein.

In various embodiments, the system 100 could apply the anatomicalmapping techniques disclosed herein to locate or detect the targetedvasculature and surrounding anatomy before, during, and/or aftertreatment.

Reference throughout this specification to “one embodiment” or “anembodiment” means that a particular feature, structure, orcharacteristic described in connection with the embodiment is includedin at least one embodiment. Thus, appearances of the phrases “in oneembodiment” or “in an embodiment” in various places throughout thisspecification are not necessarily all referring to the same embodiment.Furthermore, the particular features, structures, or characteristics maybe combined in any suitable manner in one or more embodiments.

The terms and expressions which have been employed herein are used asterms of description and not of limitation, and there is no intention,in the use of such terms and expressions, of excluding any equivalentsof the features shown and described (or portions thereof), and it isrecognized that various modifications are possible within the scope ofthe claims. Accordingly, the claims are intended to cover all suchequivalents.

INCORPORATION BY REFERENCE

References and citations to other documents, such as patents, patentapplications, patent publications, journals, books, papers, webcontents, have been made throughout this disclosure. All such documentsare hereby incorporated herein by reference in their entirety for allpurposes.

EQUIVALENTS

Various modifications of the invention and many further embodimentsthereof, in addition to those shown and described herein, will becomeapparent to those skilled in the art from the full contents of thisdocument, including references to the scientific and patent literaturecited herein. The subject matter herein contains important information,exemplification and guidance that can be adapted to the practice of thisinvention in its various embodiments and equivalents thereof.

What is claimed is:
 1. A device for treating a condition within a nasalcavity of a patient, the device comprising: a shaft; an end effectoroperably associated with the shaft and comprising an architecture in adeployed configuration; and a handle operably associated with the shaftand comprising a shape associated with the architecture of the endeffector in the deployed configuration.
 2. The device of claim 1,wherein the handle comprises a grip portion comprises a top, a bottom,sides, a proximal end, and a distal end.
 3. The device of claim 2,wherein the end effector comprises a first segment that is spaced apartfrom a second segment, each of the first and second segments istransformable between a retracted configuration and an expanded deployedconfiguration.
 4. The device of claim 3, wherein at least one of thetop, bottom, and sides of the grip portion of the handle is associatedwith architecture of at least one of the first and second segments inthe deployed configuration.
 5. The device of claim 4, wherein the firstsegment comprises a first set of flexible support elements and thesecond segment comprises a second set of flexible support elements. 6.The device of claim 5, wherein, when in the deployed configuration, thefirst set of support elements comprises a first pair of struts, eachcomprising a loop shape and extending upward and second pair of struts,each comprising a loop shape and extending downward.
 7. The device ofclaim 6, wherein the top of the grip portion is associated with theupwardly extending first pair of struts and the bottom of the gripportion is associated with the downwardly extending second pair ofstruts.
 8. The device of claim 5, wherein, when in the deployedconfiguration, the second set of support elements comprises a second setof struts, each comprising a loop shape extending outward to form anopen-ended circumferential shape and the distal end of the grip portionis associated with the outwardly extending second set of struts.
 9. Thedevice of claim 4, wherein the shape of the grip portion provides forambidextrous use for both left and right handed use and conforms to handanthropometrics to allow for at least one of an overhand grip style andan underhand grip style during use in a procedure.
 10. The device ofclaim 9, wherein the shape of the grip portion provides a user with aphysical confirmation of an orientation of the first and second segmentsof the end effector when in the deployed configurations.
 11. A methodfor treating a condition within a nasal cavity of a patient, the methodcomprising: providing a treatment device comprising a shaft, an endeffector operably associated with the shaft and comprising anarchitecture in a deployed configuration, and a handle operablyassociated with the shaft and comprising a shape associated with thearchitecture of the end effector in the deployed configuration;advancing the end effector to one or more target sites within the nasalcavity of the patient, the end effector configured for delivering energyto one or more target sites within the nasal cavity in the deployedconfiguration; positioning the end effector at the one or more targetsites based, at least in part, on orientation of the handle, deployingthe end effector at the one or more target sites; and delivering energyfrom the end effector to tissue at the one or more target sites.
 12. Themethod of claim 11, wherein the handle comprises a grip portioncomprises a top, a bottom, sides, a proximal end, and a distal end. 13.The method of claim 12, wherein the end effector comprises a firstsegment that is spaced apart from a second segment, each of the firstand second segments is transformable between a retracted configurationand an expanded deployed configuration.
 14. The method of claim 13,wherein at least one of the top, bottom, and sides of the grip portionof the handle is associated with architecture of at least one of thefirst and second segments in the deployed configuration.
 15. The methodof claim 14, wherein the first segment comprises a first set of flexiblesupport elements and the second segment comprises a second set offlexible support elements.
 16. The method of claim 15, wherein, when inthe deployed configuration, the first set of support elements comprisesa first pair of struts, each comprising a loop shape and extendingupward and second pair of struts, each comprising a loop shape andextending downward.
 17. The method of claim 16, wherein the top of thegrip portion is associated with the upwardly extending first pair ofstruts and the bottom of the grip portion is associated with thedownwardly extending second pair of struts.
 18. The method of claim 15,wherein, when in the deployed configuration, the second set of supportelements comprises a second set of struts, each comprising a loop shapeextending outward to form an open-ended circumferential shape and thedistal end of the grip portion is associated with the outwardlyextending second set of struts.
 19. The method of claim 14, wherein theshape of the grip portion provides for ambidextrous use for both leftand right handed use and conforms to hand anthropometrics to allow forat least one of an overhand grip style and an underhand grip styleduring use in a procedure.
 20. The method of claim 19, wherein the shapeof the grip portion provides a user with a physical confirmation of anorientation of the first and second segments of the end effector when inthe deployed configurations.